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Visual Defects and Ageing

  • Sergio Claudio SaccàEmail author
  • Carlo Alberto Cutolo
  • Tommaso Rossi
Chapter
Part of the Subcellular Biochemistry book series (SCBI, volume 91)

Abstract

Many diseases are related to age, among these neurodegeneration is particularly important. Alzheimer’s disease Parkinson’s and Glaucoma have many common pathogenic events including oxidative damage, Mitochondrial dysfunction, endothelial alterations and changes in the visual field. These are well known in the case of glaucoma, less in the case of neurodegeneration of the brain. Many other molecular aspects are common, such as the role of endoplasmic reticulum autophagy and neuronal apoptosis while others have been neglected due to lack of space such as inflammatory cytokine or miRNA. Moreover, the loss of specific neuronal populations, the induction of similar mechanisms of cell injury and the deposition of protein aggregates in specific anatomical areas are very similar events between these diseases. Intracellular and/or extracellular accumulation of protein aggregates is a key feature of many neurodegenerative disorders. The existence of abnormal protein aggregates has been documented in the RGCs of glaucomatous patients such as the anomalous Tau protein or the β-amyloid accumulations. Intra-cell catabolic processes also appear to be common in both glaucoma and neurodegeneration. They also help us to understand how the basis between these diseases is common and how the visual aspects can be a serious problem for those who are affected.

Keywords

Glaucoma Alzheimer’s disease Parkinson’s disease Oxidative stress Mitochondria Endothelial dysfunction Trabecular meshwork Autophagy Visual field 

Abbreviations

AC

Anterior chamber

AD

Alzheimer’s disease

AF

Actin microfilaments

AH

Aqueous humour

AMD

Age related macular degeneration

ECM

Extracellular matrix

ER

Endoplasmic reticulum

GSH

Glutathione

IF

Intermediate filaments

JCT

Juxtacanalicular connective tissue

MT

Microtubules

mtDNA

Mitochondrial DNA

NO

Nitric oxide

ONH

Optic nerve head

PD

Parkinson’s disease

PKC

Protein kinases

POAG

Primary open-angle glaucoma

RGCs

Retinal ganglion cells

RNFL

Retinal nerve fibre layer

ROS

Reactive oxygen species

ROS

Reactive oxygen species

SC

Schlemm’s canal

SOD

Superoxide dismutase

TM

Trabecular meshwork

UPR

Unfolded protein response

UV

Ultraviolet rays

Notes

Acknowledgements

The authors would like to thank Dr. Carmen Laethem for allowing us to publish her beautiful photograph of TM endothelial cells (Fig. 14.4).

References

  1. Aga M, Bradley JM, Wanchu R, Yang YF, Acott TS et al (2014) Differential effects of caveolin-1 and -2 knockdown on aqueous outflow and altered extracellular matrix turnover in caveolin-silenced trabecular meshwork cells. Invest Ophthalmol Vis Sci 55:5497–5509PubMedPubMedCentralCrossRefGoogle Scholar
  2. Agarwal S, Sohal RS (1994) Ageing and protein oxidative damage. Mech Ageing Dev 75:11–19PubMedCrossRefGoogle Scholar
  3. Aihara M, Sugawara K, Torii S, Hosaka M, Kurihara H et al (2004) Angiogenic endothelium-specific nestin expression is enhanced by the first intron of the nestin gene. Lab Investig 84:1581–1592PubMedCrossRefGoogle Scholar
  4. Al-Aswad LA, Gong H, Lee D, O’Donnell ME, Brandt JD et al (1999) Effects of Na-K-2Cl cotransport regulators on outflow facility in calf and human eyes in vitro. Invest Ophthalmol Vis Sci 40:1695–1701PubMedGoogle Scholar
  5. Alexander JP, Acott TS (2003) Involvement of the Erk-MAP kinase pathway in TNFalpha regulation of trabecular matrix metalloproteinases and TIMPs. Invest Ophthalmol Vis Sci 44:164–169PubMedCrossRefGoogle Scholar
  6. Almasieh M, Wilson AM, Morquette B, Cueva Vargas JL, Di Polo A (2012) The molecular basis of retinal ganglion cell death in glaucoma. Prog Retin Eye Res 31:152–181PubMedCrossRefGoogle Scholar
  7. Alqudah A, Mansberger SL, Gardiner SK, Demirel S (2016) Vision-related quality of life in glaucoma suspect or early glaucoma patients. J Glaucoma 25:629–633PubMedPubMedCentralCrossRefGoogle Scholar
  8. Alvarado JA, Shifera AS (2010) Progress towards understanding the functioning of the trabecular meshwork based on lessons from studies of laser trabeculoplasty. Br J Ophthalmol 94:1417–1418PubMedCrossRefGoogle Scholar
  9. Alvarado JA, Murphy CG, Polansky JR, Juster R (1981) Agerelated changes in trabecular meshwork cellularity. Invest Ophthalmol Vis Sci 21:714–727PubMedGoogle Scholar
  10. Alvarado JA, Murphy C, Juster R (1984) Trabecular meshwork cellularity in primary open-angle glaucoma and nonglaucomatous normals. Ophthalmology 91:564–579PubMedCrossRefGoogle Scholar
  11. Alvarado JA, Alvarado RG, Yeh RF, Franse-Carman L, Marcellino GR et al (2005a) A new insight into the cellular regulation of aqueous outflow: how trabecular meshwork endothelial cells drive a mechanism that regulates the permeability of Schlemm’s canal endothelial cells. Br J Ophthalmol 89:1500–1505PubMedPubMedCentralCrossRefGoogle Scholar
  12. Alvarado JA, Yeh RF, Franse-Carman L, Marcellino G, Brownstein MJ (2005b) Interactions between endothelia of the trabecular meshwork and of Schlemm’s canal: a new insight into the regulation of aqueous outflow in the eye. Trans Am Ophthalmol Soc 103:148–162PubMedPubMedCentralGoogle Scholar
  13. Ames BN, Gold LS (1991) Endogenous mutagens and the causes of ageing and cancer. Mutat Res 250:3–16PubMedCrossRefGoogle Scholar
  14. Aroca-Aguilar JD, Sánchez-Sánchez F, Ghosh S, Fernández-Navarro A, Coca-Prados M et al (2011) Interaction of recombinant myocilin with the matricellular protein SPARC: functional implications. Invest Ophthalmol Vis Sci 52:179–189PubMedPubMedCentralCrossRefGoogle Scholar
  15. Bagnis A, Izzotti A, Centofanti M, Saccà SC (2012) Aqueous humor oxidative stress proteomic levels in primary open angle glaucoma. Exp Eye Res 103:55–62PubMedCrossRefGoogle Scholar
  16. Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ et al (2016) Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature 530:184–189PubMedPubMedCentralCrossRefGoogle Scholar
  17. Balci M, Sahin S, Mutlu FM, Yağci R, Karanci P, Yildiz M (2011) Investigation of oxidative stress in pterygium tissue. Mol Vis 17:443–447PubMedPubMedCentralGoogle Scholar
  18. Baltan S, Inman DM, Danilov CA, Morrison RS, Calkins DJ et al (2010) Metabolic vulnerability disposes retinal ganglion cell axons to dysfunction in a model of glaucomatous degeneration. J Neurosci 30:5644–5652PubMedPubMedCentralCrossRefGoogle Scholar
  19. Barja G (2004) Free radicals and ageing. Trends Neurosci 27:595–600PubMedCrossRefGoogle Scholar
  20. Barnett A, Brewer GJ (2011) Autophagy in ageing and Alzheimer’s disease: pathologic or protective? J Alzheimers Dis 25:385–394PubMedPubMedCentralCrossRefGoogle Scholar
  21. Bengrine A, Li J, Awayda MS (2007) The A-kinase anchoring protein 15 regulates feedback inhibition of the epithelial Na+ channel. FASEB J 21:1189–1201PubMedCrossRefGoogle Scholar
  22. Bhatia-Dey N, Kanherkar RR, Stair SE, Makarev EO, Csoka AB (2016) Cellular senescence as the causal nexus of ageing. Front Genet 7:13PubMedPubMedCentralCrossRefGoogle Scholar
  23. Bhatnagar S, Panguluri SK, Gupta SK, Dahiya S, Lundy RF, Kumar A (2010) Tumor necrosis factor-α regulates distinct molecular pathways and gene networks in cultured skeletal muscle cells. PLoS One 5:e13262PubMedPubMedCentralCrossRefGoogle Scholar
  24. Birren JE, Fisher LM (1991) Ageing and slowing of behavior: consequences for cognition and survival. Nebr Symp Motiv 39:1–37PubMedGoogle Scholar
  25. Bishop AL, Hall A (2000) Rho GTPases and their effector proteins. Biochem J 348:241–255PubMedPubMedCentralCrossRefGoogle Scholar
  26. Black AT, Gordon MK, Heck DE, Gallo MA, Laskin DL, Laskin JD (2011) UVB light regulates expression of antioxidants and inflammatory mediators in human corneal epithelial cells. Biochem Pharmacol 81:873–880PubMedPubMedCentralCrossRefGoogle Scholar
  27. Blane A (2016) Through the looking glass: a review of the literature investigating the impact of glaucoma on crash risk, driving performance, and driver self-regulation in older drivers. J Glaucoma 25:13–21CrossRefGoogle Scholar
  28. Blanks JC, Torigoe Y, Hinton DR, Blanks RH (1996) Retinal pathology in Alzheimer’s disease. I Ganglion cell loss in foveal/parafoveal retina. Neurobiol Ageing 17:377–384CrossRefGoogle Scholar
  29. Bolacchi F, Garaci FG, Martucci A, Meschini A, Fornari M et al (2012) Differences between proximal versus distal intraorbital optic nerve diffusion tensor magnetic resonance imageing properties in glaucoma patients. Invest Ophthalmol Vis Sci 53:4191–4196PubMedCrossRefGoogle Scholar
  30. Bourne RR, Jonas JB, Flaxman SR, Keeffe J, Leasher J et al (2014) Prevalence and causes of vision loss in high-income countries and in Eastern and Central Europe: 1990–2010. Br J Ophthalmol 98:629–638PubMedCrossRefGoogle Scholar
  31. Bourne RRA, Flaxman SR, Braithwaite T, Cicinelli MV, Das A et al (2017) Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis. Lancet Glob Health 5:e888–e897PubMedCrossRefGoogle Scholar
  32. Braakman ST, Pedrigi RM, Read AT, Smith JA, Stamer WD et al (2014) Biomechanical strain as a trigger for pore formation in Schlemm’s canal endothelial cells. Exp Eye Res 127:224–235PubMedPubMedCentralCrossRefGoogle Scholar
  33. Brandt JD, O’Donnell ME (1999) How does the trabecular meshwork regulate outflow? Clues from the vascular endothelium. J Glaucoma 8:328–339PubMedCrossRefGoogle Scholar
  34. Burton R, Smith ND, Crabb DP (2014) Eye movements and reading in glaucoma: observations on patients with advanced visual field loss. Graefes Arch Clin Exp Ophthalmol 252:1621–1630PubMedCrossRefGoogle Scholar
  35. Calkins DJ (2013) Age-related changes in the visual pathways: blame it on the axon. Invest Ophthalmol Vis Sci 54:37–41CrossRefGoogle Scholar
  36. Cargnello M, Roux PP (2011) Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 75:50–83PubMedPubMedCentralCrossRefGoogle Scholar
  37. Cassels NK, Wild JM, Margrain TH, Chong V, Acton JH (2018) The use of microperimetry in assessing visual function in age-related macular degeneration. Surv Ophthalmol 63:40–55PubMedCrossRefGoogle Scholar
  38. Chauhan BC, Garway-Heath DF, Goni FJ, Rossetti L, Bengtsson B et al (2008) Practical recommendations for measuring rates of visual field change in glaucoma. Br J Ophthalmol 92:569–573PubMedPubMedCentralCrossRefGoogle Scholar
  39. Chen PP (2003) Blindness in patients with treated open-angle glaucoma. Ophthalmology 110:726–733PubMedCrossRefGoogle Scholar
  40. Chen Y, Wang Y, Yu H, Wang F, Xu W (2005) The cross talk between protein kinase A- and RhoA-mediated signaling in cancer cells. Exp Biol Med (Maywood) 230:731–741CrossRefGoogle Scholar
  41. Cheung ZH, Yip HK, Wu W, So KF (2003) Axotomy induces cytochrome c release in retinal ganglion cells. Neuroreport 14:279–282PubMedCrossRefGoogle Scholar
  42. Chi X, Wang S, Huang Y, Stamnes M, Chen JL (2013) Roles of rho GTPases in intracellular transport and cellular transformation. Int J Mol Sci 14:7089–7108PubMedPubMedCentralCrossRefGoogle Scholar
  43. Choi DW (1988) Glutamate neurotoxicity and diseases of the nervous system. Neuron 1:623–634PubMedCrossRefPubMedCentralGoogle Scholar
  44. Choi SI, Kim TI, Kim KS, Kim BY, Ahn SY et al (2009) Decreased catalase expression and increased susceptibility to oxidative stress in primary cultured corneal fibroblasts from patients with granular corneal dystrophy type II. Am J Pathol 175:248–261PubMedPubMedCentralCrossRefGoogle Scholar
  45. Coca-Prados M, Ghosh S (2008). Functional modulators linking inflow with outflow of aqueous humor. In: Civan M (ed) In the eye’s aqueous humour, 2nd edn. Curr Topics Membr 5:123–160. Vol. 62, ElsevierGoogle Scholar
  46. Colledge M, Scott JD (1999) AKAPs from structure to function. Trends Cell Biol 9:216–221PubMedCrossRefGoogle Scholar
  47. Coppé JP, Patil CK, Rodier F, Sun Y, Muñoz DP et al (2008) Senescence-associated secretory phenotypes reveal cell-Nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol e301:6Google Scholar
  48. Cordeiro MF, Guo L, Luong V, Harding G, Wang W et al (2004) Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration. Proc Natl Acad Sci U S A 101:13352–13356PubMedPubMedCentralCrossRefGoogle Scholar
  49. Cory GOC, Cramer R, Blanchoin L, Ridley AJ (2003) Phosphorylation of the WASP-VCA domain increases its affinity for the Arp2/3 complex and enhances actin polymerization by WASP. Mol Cell 11:1229–1239PubMedCrossRefGoogle Scholar
  50. Costarides AP, Riley MV, Green K (1991) Roles of catalase and the glutathione redox cycle in the regulation of anterior-chamber hydrogen peroxide. Ophthalmic Res 23:284–294PubMedCrossRefGoogle Scholar
  51. Crabb DP (2016) A view on glaucoma – are we seeing it clearly? Eye (Lond) 30:304–313CrossRefGoogle Scholar
  52. Crabb DP, Smith ND, Glen FC, Burton R, Garway-Heath DF (2013) How does glaucoma look?: patient perception of visual field loss. Ophthalmology 120:1120–1126PubMedCrossRefGoogle Scholar
  53. Cuervo AM, Stefanis L, Fredenburg R, Lansbury PT, Sulzer D (2004) Impaired degradation of mutant α-synuclein by chaperone-mediated autophagy. Science 305:1292–1295PubMedCrossRefGoogle Scholar
  54. Cullinan SB, Diehl JA (2006) Coordination of ER and oxidative stress signaling: the PERK/Nrf2 signaling pathway. Int J Biochem Cell Biol 38:317–332PubMedCrossRefGoogle Scholar
  55. Curcio CA, Millican CL, Allen KA, Kalina RE (1993) Ageing of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina. Invest Ophthalmol Vis Sci 34:3278–3296PubMedGoogle Scholar
  56. Dan Dunn J, Alvarez LA, Zhang X, Soldati T (2015) Reactive oxygen species and mitochondria: a nexus of cellular homeostasis. Redox Biol 6:472–485PubMedPubMedCentralCrossRefGoogle Scholar
  57. de Magalhães JP, Passos JF (2017) Stress, cell senescence and organismal ageing. Mech Ageing Dev S0047–6374:30078–30077Google Scholar
  58. Dismuke WM, Mbadugha CC, Ellis DZ (2008) NO-induced regulation of human trabecular meshwork cell volume and aqueous humor outflow facility involve the BKCa ion channel. Am J Physiol Cell Physiol 294:C1378–C1386PubMedCrossRefGoogle Scholar
  59. Diviani D, Scott JD (2001) AKAP signaling complexes at the cytoskeleton. J Cell Sci 114:1431–1437PubMedGoogle Scholar
  60. Diviani D, Soderling J, Scott JD (2001) AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation. J Biol Chem 276:44247–44257PubMedCrossRefGoogle Scholar
  61. Djabali K (1999) Cytoskeletal proteins connecting intermediate filaments to cytoplasmic and nuclear periphery. Histol Histopathol 14:501–509PubMedGoogle Scholar
  62. Dreyer EB, Grosskreutz CL (1997) Excitatory mechanisms in retinal ganglion cell death in primary open angle glaucoma (POAG). Clin Neurosci 4:270–273PubMedGoogle Scholar
  63. Dumont P, Burton M, Chen QM, Gonos ES, Frippiat C et al (2000) Induction of replicative senescence biomarkers by sublethal oxidative stresses in normalhuman fibroblast. Free Radic Biol Med 28:361–373PubMedCrossRefGoogle Scholar
  64. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516PubMedPubMedCentralCrossRefGoogle Scholar
  65. El-Remessy AB, Tawfik HE, Matragoon S, Pillai B, Caldwell RB et al (2010) Peroxynitrite mediates diabetes-induced endothelial dysfunction: possible role of Rho kinase activation. Exp Diabetes Res 247861:2010Google Scholar
  66. Epstein DL, Rohen JW (1991) Morphology of the trabecular meshwork and inner-wall endothelium after cationized ferritin perfusion in the monkey eye. Invest Ophthalmol Vis Sci 32:160–171PubMedGoogle Scholar
  67. Eriksson EE, Xie X, Werr J, Thoren P, Lindbom L (2001) Direct viewing of atherosclerosis in vivo: plaque invasion by leukocytes is initiated by the endothelial selectins. FASEB J 15:1149–1157PubMedCrossRefGoogle Scholar
  68. Erusalimsky JD, Skene C (2009) Mechanisms of endothelial senescence. Exp Physiol 94:299–304PubMedCrossRefGoogle Scholar
  69. Fine BS, Yanoff M, Stone RA (1981) A clinicopathologic study of four cases of primary open-angle glaucoma compared to normal eyes. Am J Ophthalmol 91:88–105PubMedCrossRefGoogle Scholar
  70. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247PubMedCrossRefGoogle Scholar
  71. Flatt T (2012) A new definition of ageing? Front Genet 3:148PubMedPubMedCentralCrossRefGoogle Scholar
  72. Forte G, Minieri M, Cossa P, Antenucci D, Sala M et al (2006) Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation. Stem Cells 24:23–33PubMedCrossRefGoogle Scholar
  73. Francis SH, Corbin JD (1994) Structure and function of cyclic nuleotide-dependent protein kinases. Annu Rev Physiol 56:237–272PubMedCrossRefGoogle Scholar
  74. Frippiat C, Chen QM, Zdanov S, Magalhaes JP, Remacle J et al (2001) Subcytotoxic H2O2 stress triggers a release of transforming growthfactor-beta1, which induces biomarkers of cellular senescence of humandiploid fibroblasts. J Biol Chem 276:2531–2537PubMedCrossRefGoogle Scholar
  75. Frojdman K, Pelliniemi L, Lendahl U, Virtanen I, Eriksson JE (1997) The intermediate filament protein nestin occurs transiently in differentiating testis of rat and mouse. Differentiation 61:243–249PubMedCrossRefGoogle Scholar
  76. Fuchs E, Yang Y (1999) Crossroads on cytoskeletal highways. Cell 98:547–550PubMedCrossRefGoogle Scholar
  77. Gardiner SK, Crabb DP (2002) Frequency of testing for detecting visual field progression. Br J Ophthalmol 86:560–564PubMedPubMedCentralCrossRefGoogle Scholar
  78. Girkin CA, McGwin G Jr, Sinai MJ, Sekhar GC, Fingeret M et al (2011) Variation in optic nerve and macular structure with age and race with spectral-domain optical coherence tomography. Ophthalmology 118:2403–2408PubMedCrossRefGoogle Scholar
  79. Glen FC, Crabb DP, Smith ND, Burton R, Garway-Heath DF (2012) Do patients with glaucoma have difficulty recognizing faces? Invest Ophthalmol Vis Sci 53:3629–3637PubMedCrossRefGoogle Scholar
  80. Gogg S, Smith U, Jansson PA (2009) Increased MAPK activation and impaired insulin signaling in subcutaneous microvascular endothelial cells in type 2 diabetes: the role of endothelin-1. Diabetes 58:2238–2245PubMedPubMedCentralCrossRefGoogle Scholar
  81. Gong H, Freddo TF, Johnson M (1992) Age-related changes of sulfated proteoglycans in the normal human trabecular meshwork. Exp Eye Res 55:691–709PubMedCrossRefGoogle Scholar
  82. Gong H, Overby D, Ruberti J, Freddo T, Johnson M (2001) Human outflow pathway viewed by quick freeze deep etch. Invest Ophthalmol Vis Sci 42:S749Google Scholar
  83. Gong H, Ruberti J, Overby D, Johnson M, Freddo TF (2002) A new view of the human trabecular meshwork using quick-freeze, deep-etch electron microscopy. Exp Eye Res 75:347–358PubMedCrossRefGoogle Scholar
  84. Gorbatyuk M, Gorbatyuk O (2013) Review: retinal degeneration: focus on the unfolded protein response. Mol Vis 19:1985–1998PubMedPubMedCentralGoogle Scholar
  85. Gracitelli CP, Abe RY, Tatham AJ, Rosen PN, Zangwill LM et al (2015) Association between progressive retinal nerve fiber layer loss and longitudinal change in quality of life in glaucoma. JAMA Ophthalmol 133:384–390PubMedPubMedCentralCrossRefGoogle Scholar
  86. Gupta N, Yücel YH (2001) Glaucoma and the brain. J Glaucoma 10:S28–S29PubMedCrossRefGoogle Scholar
  87. Hailey DW, Rambold AS, Satpute-Krishnan P, Mitra K, Sougrat R et al (2010) Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141:656–667PubMedPubMedCentralCrossRefGoogle Scholar
  88. Hall A (1998) Rho GTPases and the actin cytoskeleton. Science 279:509–514PubMedPubMedCentralCrossRefGoogle Scholar
  89. Harada C, Nakamura K, Namekata K, Okumura A, Mitamura Y et al (2006) Role of apoptosis signal-regulating kinase 1 in stress-induced neural cell apoptosis in vivo. Am J Pathol 168:261–269PubMedPubMedCentralCrossRefGoogle Scholar
  90. Harada C, Namekata K, Guo X, Yoshida H, Mitamura Y et al (2010) ASK1 deficiency attenuates neural cell death in GLAST-deficient mice, a model of normal tension glaucoma. Cell Death Differ 17:1751–1759PubMedCrossRefGoogle Scholar
  91. Hayakawa M, Hattori K, Sugiyama S, Ozawa T (1992) Age associated oxygen damage and mutations in mitochondrial DNA in human hearts. Biochem Biophys Res Commun 189:979–985PubMedCrossRefGoogle Scholar
  92. Haymes SA, LeBlanc RP, Nicolela MT, Chiasson LA, Chauhan BC (2008) Glaucoma and on-road driving performance. Invest Ophthalmol Vis Sci 49:3035–3041PubMedCrossRefGoogle Scholar
  93. He Y, Ge J, Tombran-Tink J (2008) Mitochondrial defects and dysfunction in calcium regulation in glaucomatous trabecular meshwork cells. Invest Ophthalmol Vis Sci 49:4912–4922PubMedCrossRefGoogle Scholar
  94. Heijl A, Lindgren A, Lindgren G (1989) Test–retest variability in glaucomatous visual fields. Am J Ophthalmol 108:130–135PubMedCrossRefGoogle Scholar
  95. Heijl A, Buchholz P, Norrgren G, Bengtsson B (2012) Rates of visual field progression in clinical glaucoma care. Acta Ophthalmol 91:406–412PubMedPubMedCentralCrossRefGoogle Scholar
  96. Hendrickson ML, Rao AJ, Demerdash ON, Kalil RE (2011) Expression of nestin by neural cells in the adult rat and human brain. PLoS One 6:e18535PubMedPubMedCentralCrossRefGoogle Scholar
  97. Hewitt G, Jurk D, Marques FDM, Correia-Melo C, Hardy T et al (2012) Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence. Nat Commun 3:708PubMedPubMedCentralCrossRefGoogle Scholar
  98. Honig LS, Rosenberg RN (2000) Apoptosis and neurologic disease. Am J Med 108:317–330PubMedCrossRefGoogle Scholar
  99. Huang LJ, Durick K, Weiner JA, Chun J, Taylor SS (1997) D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain. Proc Natl Acad Sci U S A 94:11184–11189PubMedPubMedCentralCrossRefGoogle Scholar
  100. Ikehata H, Ono T (2011) The mechanisms of UV mutagenesis. J Radiat Res (Tokyo) 52:115–125CrossRefGoogle Scholar
  101. Iseri PK, Altinaş O, Tokay T, Yüksel N (2006) Relationship between cognitive impairment and retinal morphological and visual functional abnormalities in Alzheimer disease. J Neuroophthalmol 26:8–24CrossRefGoogle Scholar
  102. Izzotti A (2009) Gene environment interactions in noncancer degenerative diseases. Mutat Res Fundam Mol Mech Mutagen 667:1–3CrossRefGoogle Scholar
  103. Izzotti A, Sacca SC, Cartiglia C, De Flora S (2003) Oxidative deoxyribonucleic acid damage in the eyes of glaucoma patients. Am J Med 114:638e646CrossRefGoogle Scholar
  104. Izzotti A, Saccà SC, Longobardi M, Cartiglia C (2009) Sensitivity of ocular anterior chamber tissues to oxidative damage and its relevance to the pathogenesis of glaucoma. Invest Ophthalmol Vis Sci 50:5251–5258PubMedCrossRefGoogle Scholar
  105. Izzotti A, Longobardi M, Cartiglia C, Saccà SC (2010a) Proteome alterations in primary open angle glaucoma aqueous humor. J Proteome Res 9:4831–4838PubMedCrossRefGoogle Scholar
  106. Izzotti A, Saccà SC, Longobardi M, Cartiglia C (2010b) Mitochondrial damage in the trabecular meshwork of patients with glaucoma. Arch Ophthalmol 128:724–730PubMedCrossRefGoogle Scholar
  107. Izzotti A, Longobardi M, Cartiglia C, Saccà SC (2011) Mitochondrial damage in the trabecular meshwork occurs only in primary open-angle glaucoma and in pseudoexfoliative glaucoma. PLoS One 6:e14567PubMedPubMedCentralCrossRefGoogle Scholar
  108. Jayadev S, Petranka JG, Cheran SK, Biermann JA, Barrett JC et al (1999) Reduced capacitative calcium entry correlates with vesicle accumulation and apoptosis. J Biol Chem 274:8261–8268PubMedCrossRefGoogle Scholar
  109. Joe MK, Tomarev SI (2010) Expression of myocilin mutants sensitizes cells to oxidative stress-induced apoptosis: implication for glaucoma pathogenesis. Am J Pathol 176:2880–2890PubMedPubMedCentralCrossRefGoogle Scholar
  110. Johansen T, Lamark T (2011) Selective autophagy mediated by autophagic adapter proteins. Autophagy 7:279e296CrossRefGoogle Scholar
  111. Johnson M, Erickson K (2000) Aqueous humor and the dynamics of its flow. In: Albert DM, Jakobiec FA (eds) Principles and practice of ophthalmology. Saunders, Philadelphia, pp 2577–2595Google Scholar
  112. Johnson BM, Miao M, Sadun AA (1987) Age-related decline of human optic nerve axon populations. Age (Omaha) 10:5–9CrossRefGoogle Scholar
  113. Jones L, Bryan SR, Crabb DP (2017) Gradually then suddenly? Decline in vision-related quality of life as glaucoma worsens. J Ophthalmol 2017:1621640PubMedPubMedCentralCrossRefGoogle Scholar
  114. Joshi MB, Philippova M, Ivanov D, Allenspach R, Erne P, Resink TJ (2005) T-cadherin protects endothelial cells from oxidative stress-induced apoptosis. FASEB J 19:1737–1739PubMedCrossRefGoogle Scholar
  115. Joyce NC, Zhu CC, Harris DL (2009) Relationship among oxidative stress, DNA damage, and proliferative capacity in human corneal endothelium. Invest Ophthalmol Vis Sci 50:2116–2122PubMedCrossRefGoogle Scholar
  116. Jurkunas UV, Bitar MS, Funaki T, Azizi B (2010) Evidence of oxidative stress in the pathogenesis of fuchs endothelial corneal dystrophy. Am J Pathol 177:2278–2289PubMedPubMedCentralCrossRefGoogle Scholar
  117. Kachinsky AM, Dominov JA, Miller JB (1994) Myogenesis and the intermediate filament protein, nestin. Dev Biol 165:216–228PubMedCrossRefGoogle Scholar
  118. Kania E, Pająk B, Orzechowski A (2015) Calcium homeostasis and ER stress in control of autophagy in cancer cells. Biomed Res Int 2015:352794PubMedPubMedCentralCrossRefGoogle Scholar
  119. Karar J, Maity A (2011) PI3K/AKT/mTOR Pathway in Angiogenesis. Front Mol Neurosci 4:51Google Scholar
  120. Keller KE, Kelley MJ, Acott TS (2007) Extracellular matrix gene alternative splicing by trabecular meshwork cells in response to mechanical stretching. Invest Ophthalmol Vis Sci 48:1164–1172PubMedCrossRefGoogle Scholar
  121. Keller J, Sánchez-Dalmau BF, Villoslada P (2014) Lesions in the posterior visual pathway promote trans-synaptic degeneration of retinal ganglion cells. PLoS One 9:e97444PubMedPubMedCentralCrossRefGoogle Scholar
  122. Khurana RN, Deng PF, Epstein DL, Vasantha Rao P (2003) The role of protein kinase C in modulation of aqueous humor outflow facility. Exp Eye Res 76:39–47PubMedCrossRefGoogle Scholar
  123. Kikuchi M, Tenneti L, Lipton SA (2000) Role of p38 mitogen-activated protein kinase in axotomy-induced apoptosis of rat retinal ganglion cells. J Neurosci 20:5037–5044PubMedCrossRefGoogle Scholar
  124. Kilpatrick BS, Eden ER, Schapira AH, Futter CE, Patel S (2013) Direct mobilization of lysosomal Ca2+ triggers complex Ca2+ signals. J Cell Sci 126:60–66PubMedCrossRefGoogle Scholar
  125. Kim M, Ho A, Lee JH (2017) Autophagy and human neurodegenerative diseases-A fly’s perspective. Int J Mol Sci 18(7):E1596PubMedCrossRefGoogle Scholar
  126. Koch MA, Rosenhammer B, Koschade SE, Braunger BM, Volz C et al (2014) Myocilin modulates programmed cell death during retinal development. Exp Eye Res 125:41e52CrossRefGoogle Scholar
  127. Kohno H, Sakai T, Kitahara K (2006) Induction of nestin, Ki-67, and cyclin D1 expression in Muller cells after laser injury in adult rat retina., Graefes Arch. Clin Exptl Ophthalmol 244:90–95CrossRefGoogle Scholar
  128. Kong GY, Van Bergen NJ, Trounce IA, Crowston JG (2009) Mitochondrial dysfunction and glaucoma. J Glaucoma 18:93–100PubMedCrossRefGoogle Scholar
  129. Konstas AG, Katsanos A, Quaranta L, Mikropoulos DG, Tranos PG et al (2015) Twenty-four hour efficacy of glaucoma medications. Prog Brain Res 221:297–318PubMedCrossRefGoogle Scholar
  130. Korth M, Horn F, Storck B, Jonas JB (1989) Spatial and spatiotemporal contrast sensitivity of normal and glaucoma eyes. Graefes Arch Clin Exp Ophthalmol 227:428–435PubMedCrossRefGoogle Scholar
  131. Kotecha A, O’Leary N, Melmoth D, Grant S, Crabb DP (2009) The functional consequences of glaucoma for eye-hand coordination. Invest Ophthalmol Vis Sci 50:203–213PubMedCrossRefGoogle Scholar
  132. Kotecha A, Richardson G, Chopra R, Fahy RTA, Garway-Heath DF et al (2012) Balance control in glaucoma. Invest Ophthalmol Vis Sci 53:7795–7801PubMedCrossRefGoogle Scholar
  133. Kuleshova ON, Nepomnyashchikh GI, Aidagulova SV, Shvedova EV (2008) Ultrastructure of the endothelium of the drainage system of the eye. Bull Exp Biol Med 145:634–637PubMedCrossRefGoogle Scholar
  134. Kumar A (2016) Editorial (Thematic selection): mitochondrial dysfunction & neurological disorders. Curr Neuropharmacol 14:565–566PubMedPubMedCentralCrossRefGoogle Scholar
  135. Kusbeci T, Kusbeci OY, Mas NG, Karabekir HS, Yavas G et al (2015) Stereological evaluation of the optic nerve volume in Alzheimer disease. Surgery 26:1683–1686Google Scholar
  136. Kwon HS, Nakaya N, Abu-Asab M, Kim HS, Tomarev SI (2014) Myocilin is involved in NgR1/Lingo-1-mediated oligodendrocyte differentiation and myelination of the optic nerve. J Neurosci 34:5539e5551CrossRefGoogle Scholar
  137. Lang P, Gesbert F, Delespine-Carmagnat M, Stancou R, Pouchelet M et al (1996) Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes. EMBO J 15:510–519PubMedPubMedCentralCrossRefGoogle Scholar
  138. Lanzetti L (2007) Actin in membrane trafficking. Curr Opin Cell Biol 19:453–458PubMedCrossRefGoogle Scholar
  139. Lee JH, Yu WH, Kumar A, Lee S, Mohan PS et al (2010) Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141:1146–1158PubMedPubMedCentralCrossRefGoogle Scholar
  140. Lepple-Wienhues A, Stahl F, Wiederholt M (1991) Differential smooth muscle-like contractile properties of trabecular meshwork and ciliary muscle. Exp Eye Res 53:33–38PubMedCrossRefGoogle Scholar
  141. Li G, Luna C, Qiu J, Epstein DL, Gonzalez P (2009) Alterations in microRNA expression in stress-induced cellular senescence. Mech Ageing Dev 130:731–741PubMedPubMedCentralCrossRefGoogle Scholar
  142. Li G, Luna C, Qiu J, Epstein DL, Gonzalez P (2011) Role of miR-204 in the regulation of apoptosis, endoplasmic reticulum stress response, and inflammation in human trabecular meshwork cells. Invest Ophthalmol Vis Sci 52:2999–3007PubMedPubMedCentralCrossRefGoogle Scholar
  143. Li WW, Li J, Bao JK (2012) Microautophagy: lesser-known self-eating. Cell Mol Life Sci 69:1125–1136PubMedCrossRefGoogle Scholar
  144. Lingor P, Koeberle P, Kügler S, Bähr M (2005) Down-regulation of apoptosis mediators by RNAi inhibits axotomy-induced retinal ganglion cell death in vivo. Brain 128:550–558PubMedCrossRefGoogle Scholar
  145. Liton PB, Challa P, Stinnett S, Luna C, Epstein DL et al (2005) Cellular senescence in the glaucomatous outflow pathway. Exp Gerontol 40:745–748PubMedPubMedCentralCrossRefGoogle Scholar
  146. Loewenfeld IE (1979) Pupillary changes related to age. In: Thompson HS (ed) Topics in neuro-ophthalmolgy. Williams & Wilkins, Baltimore, pp 124–150Google Scholar
  147. Lorenzo M, Fernández-Veledo S, Vila-Bedmar R, Garcia-Guerra L et al (2008) Insulin resistance induced by tumor necrosis factor-alpha in myocytes and brown adipocytes. J Anim Sci 86:E94–E104PubMedCrossRefGoogle Scholar
  148. Lucas DR, Newhouse JP (1957) The toxic effect of sodium L-glutamate on the inner layers of the retina. AMA Arch Ophthalmol 58:193–201PubMedCrossRefGoogle Scholar
  149. Luu CD, Dimitrov PN, Wu Z, Ayton LN, Makeyeva G et al (2013) Static and flicker perimetry in age-related macular degeneration. Invest Ophthalmol Vis Sci 54:3560–3568PubMedCrossRefGoogle Scholar
  150. Machesky LM, Reeves E, Wientjes F, Mattheyse FJ, Grogan A et al (1997) Mammalian actin-related protein 2/3 complex localizes to regions of lamellipodial protrusion and is composed of evolutionarily conserved proteins. Biochem J 328:105–112PubMedPubMedCentralCrossRefGoogle Scholar
  151. Madeo F, Tavernarakis N, Kroemer G (2010) Can autophagy promote longevity? Nat Cell Biol 12:842–846PubMedCrossRefGoogle Scholar
  152. Mao M, Hedberg-Buenz A, Koehn D, John SW, Anderson MG (2011) Anterior segment dysgenesis and early-onset glaucoma in nee mice with mutation of Sh3pxd2b. Invest Ophthalmol Vis Sci 52:2679–2688PubMedPubMedCentralCrossRefGoogle Scholar
  153. Mecocci P, MacGarvey U, Kaufman AE, Koontz D, Shoffner JM et al (1993) Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann Neurol 34:609–616PubMedCrossRefGoogle Scholar
  154. Medina RJ, Kataoka K, Takaishi M et al (2006) Isolation of epithelial stem cells from dermis by a three-dimensional culture system. J Cell Biochem 98:174–184PubMedCrossRefGoogle Scholar
  155. Meister M (1996) Multineuronal codes in retinal signaling. Proc Natl Acad Sci U S A 93:609–614PubMedPubMedCentralCrossRefGoogle Scholar
  156. Meister M, Berry MJ 2nd (1999) The neural code of the retina. Neuron 22:435–450PubMedCrossRefGoogle Scholar
  157. Mendoza-Santiesteban CE, Gabilondo I, Palma JA, Norcliffe-Kaufmann L, Kaufmann H (2017) The retina in multiple system atrophy: systematic review and meta-analysis. Front Neurol 8:206PubMedPubMedCentralCrossRefGoogle Scholar
  158. Mimura T, Kaji Y, Noma H, Funatsu H, Okamoto S (2013) The role of SIRT1 in ocular ageing. Exp Eye Res 116:17–26PubMedCrossRefGoogle Scholar
  159. Mitchell CH, Fleischhauer JC, Stamer WD, Peterson-Yantorno K, Civan MM (2002) Human trabecular meshwork cell volume regulation. Am J Physiol Cell Physiol 283:C315–C326PubMedCrossRefGoogle Scholar
  160. Mitchell JR, Oliveira C, Tsiouris AJ, Dinkin MJ (2015) Corresponding ganglion cell atrophy in patients with postgeniculate homonymous visual field loss. J Neuroophthalmol 35:353–359PubMedCrossRefGoogle Scholar
  161. Mokrý J, Cízková D, Filip S, Ehrmann J, Osterreicher J et al (2004) Nestin expression by newly formed human blood vessels. Stem Cells Dev 13:658–664PubMedCrossRefGoogle Scholar
  162. Montagnani M, Ravichandran LV, Chen H, Esposito DL, Quon MJ (2002) Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells. Mol Endocrinol 16:1931–1942PubMedCrossRefGoogle Scholar
  163. Moreau V, Tatin F, Varon C, Génot E (2003) Actin can reorganize into podosomes in aortic endothelial cells, a process controlled by Cdc42 and RhoA. Mol Cell Biol 23:6809–6822PubMedPubMedCentralCrossRefGoogle Scholar
  164. Morris MA (1990) Mitochondrial mutations in neuro-ophthalmological diseases. Rev J Clin Neuroophthalmol 10:159–166Google Scholar
  165. Morrone LA, Rombolà L, Corasaniti MT, Bagetta G, Nucci C et al (2015) Natural compounds and retinal ganglion cell neuroprotection. Prog Brain Res 220:257–281PubMedCrossRefGoogle Scholar
  166. Morselli E, Maiuri MC, Markaki M, Megalou E, Pasparaki A et al (2010) The life span-prolonging effect of sirtuin-1 is mediated by autophagy. Autophagy 6:186–188PubMedCrossRefGoogle Scholar
  167. Muriach M, Flores-Bellver M, Romero FJ, Barcia JM (2014) Diabetes and the brain: oxidative stress, inflammation, and autophagy. Oxid Med Cell Longev 2014:102158PubMedPubMedCentralCrossRefGoogle Scholar
  168. Nair RR, Solway J, Boyd DD (2006) Expression cloning identifies transgelin (SM22) as a novel repressor of 92-kDa type IV collagenase (MMP-9) expression. J Biol Chem 281:26424–26436PubMedCrossRefGoogle Scholar
  169. Narita M, Nuñez S, Heard E, Narita M, Lin AW et al (2003) Rb-Mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113:703–716PubMedCrossRefGoogle Scholar
  170. Neufeld AH, Gachie EN (2003) The inherent, age-dependent loss of retinal ganglion cells is related to the lifespan of the species. Neurobiol Ageing 24:167–172CrossRefGoogle Scholar
  171. Nickells RW (1999) Apoptosis of retinal ganglion cells in glaucoma: an update of the molecular pathways involved in cell death. Surv Ophthalmol 43:S151–S161PubMedCrossRefGoogle Scholar
  172. Nucci C, Martucci A, Mancino R, Cerulli L (2013) Glaucoma progression associated with Leber’s hereditary optic neuropathy. Int Ophthalmol 33:75–77PubMedCrossRefGoogle Scholar
  173. O’Donnell ME, Brandt JD, Curry FR (1995) Na-K-Cl cotransport regulates intracellular volume and monolayer permeability of trabecular meshwork cells. Am J Physiol Cell Physiol 268:C1067–C1074CrossRefGoogle Scholar
  174. Oh DJ, Kang MH, Ooi YH, Choi KR, Sage EH, Rhee DJ (2013) Overexpression of SPARC in human trabecular meshwork increases intraocular pressure and alters extracellular matrix. Invest Ophthalmol Vis Sci 54:3309–3319PubMedPubMedCentralCrossRefGoogle Scholar
  175. Ota H, Akishita M, Eto M, Iijima K, Kaneki M et al (2007) Sirt1 modulates premature senescence-like phenotype in human endothelial cells. J Mol Cell Cardiol 43:571–579PubMedCrossRefGoogle Scholar
  176. Ota H, Eto M, Kano MR, Kahyo T, Setou M et al (2010) Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway. Arterioscler Thromb Vasc Biol 30:2205–2211PubMedCrossRefGoogle Scholar
  177. Owsley C (2011) Ageing and vision. Vis Res 51:1610–1622PubMedCrossRefGoogle Scholar
  178. Owsley C (2016) Vision and ageing. Annu Rev Vis Sci 2:255–271PubMedCrossRefGoogle Scholar
  179. Owsley C, Huisingh C, Jackson GR, Curcio CA, Szalai AJ et al (2014) Associations between abnormal rodmediated dark adaptation and health and functioning in older adults with normal macular health. Invest Ophthalmol Vis Sci 55:4776–4789PubMedPubMedCentralCrossRefGoogle Scholar
  180. Parikh RS, Parikh SR, Sekhar GC, Prabakaran S, Babu JG et al (2007) Normal age-related decay of retinal nerve fiber layer thickness. Ophthalmology 114:921–926PubMedCrossRefGoogle Scholar
  181. Park BC, Tibudan M, Samaraweera M, Shen X, Yue BY (2007) Interaction between two glaucoma genes, optineurin and myocilin. Genes Cells 12:969–979PubMedCrossRefGoogle Scholar
  182. Pascolini D, Mariotti SP (2012) Global estimates of visual impairment. Br J Ophthalmol 96:614–618PubMedCrossRefGoogle Scholar
  183. Patel S, Muallem S (2011) Acidic Ca(2+) stores come to the fore. Cell Calcium 50:109–112PubMedCrossRefGoogle Scholar
  184. Plaza-Zabala A, Sierra-Torre V, Sierra A (2017) Autophagy and microglia: novel partners in neurodegeneration and ageing. Int J Mol Sci 18(3)Google Scholar
  185. Porter K, Nallathambi J, Lin Y, Liton PB (2013) Lysosomal basification and decreased autophagic flux in oxidatively stressed trabecular meshwork cells: implications for glaucoma pathogenesis. Autophagy 9:581–594PubMedPubMedCentralCrossRefGoogle Scholar
  186. Porter K, Hirt J, Stamer WD, Liton PB (2015) Autophagic dysregulation in glaucomatous trabecular meshwork cells. Biochim Biophys Acta 1852:379–385PubMedCrossRefGoogle Scholar
  187. Prentice H, Modi JP, Wu JY (2015) Mechanisms of neuronal protection against excitotoxicity, endoplasmic reticulum stress, and mitochondrial dysfunction in stroke and neurodegenerative diseases. Oxid Med Cell Longev 2015:964518PubMedPubMedCentralCrossRefGoogle Scholar
  188. Pryde KR, Taanman JW, Schapira AH (2016) A LON-ClpP proteolytic axis degrades complex I to extinguish ROS production in depolarized mitochondria. Cell Rep 17:2522–2531PubMedPubMedCentralCrossRefGoogle Scholar
  189. Pulliero A, Seydel A, Camoirano A, Saccà SC, Sandri M et al (2014) Oxidative damage and autophagy in the human trabecular meshwork as related with ageing. PLoS One 9:e98106PubMedPubMedCentralCrossRefGoogle Scholar
  190. Qiu Y, Shen X, Shyam R, Yue BY, Ying H (2014) Cellular processing of myocilin. PLoS One 9:e92845PubMedPubMedCentralCrossRefGoogle Scholar
  191. Qu J, Wang D, Grosskreutz CL (2010) Mechanisms of retinal ganglion cell injury and defense in glaucoma. Exp Eye Res 91:48–53PubMedPubMedCentralCrossRefGoogle Scholar
  192. Rao RV, Ellerby HM, Bredesen DE (2004) Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ 11:372–380PubMedCrossRefGoogle Scholar
  193. Rashid HO, Yadav RK, Kim HR, Chae HJ (2015) ER stress: autophagy induction, inhibition and selection. Autophagy 11:1956–1977PubMedPubMedCentralCrossRefGoogle Scholar
  194. Reid MB, Moylan JS (2011) Beyond atrophy: redox mechanisms of muscle dysfunction in chronic inflammatory disease. J Physiol 589:2171–2179PubMedPubMedCentralCrossRefGoogle Scholar
  195. Renieri G, Choritz L, Rosenthal R, Meissner S, Pfeiffer N et al (2008) Effects of endothelin-1 on calcium independent contraction of bovine trabecular meshwork. Graefes Arch Clin Exp Ophthalmol 246:1107–1115PubMedCrossRefGoogle Scholar
  196. Rodier F, Campisi J (2011) Four faces of cellular senescence. J Cell Biol 192:547–556PubMedPubMedCentralCrossRefGoogle Scholar
  197. Rubinsztein DC, Mariño G, Kroemer G (2011) Autophagy and ageing. Cell 146:682–695PubMedCrossRefGoogle Scholar
  198. Rubinsztein DC, Shpilka T, Elazar Z (2012) Mechanisms of autophagosome biogenesis. Curr Biol 22:R29–R34PubMedCrossRefGoogle Scholar
  199. Rudolph T, Frisén L (2007) Influence of ageing on visual field defects due to stable lesions. Br J Ophthalmol 91:1276–1278PubMedPubMedCentralCrossRefGoogle Scholar
  200. Russo R, Nucci C, Corasaniti MT, Bagetta G, Morrone LA (2015) Autophagy dysregulation and the fate of retinal ganglion cells in glaucomatous optic neuropathy. Prog Brain Res 220:87–105PubMedCrossRefGoogle Scholar
  201. Rutkowski P, May CA (2017) The peripheral and Central Humphrey visual field – morphological changes during ageing. BMC Ophthalmol 17:127PubMedPubMedCentralCrossRefGoogle Scholar
  202. Saccà SC, Izzotti A (2008) Oxidative stress and glaucoma: injury in the anterior segment of the eye. Prog Brain Res 173:385–407PubMedCrossRefGoogle Scholar
  203. Saccà SC, Izzotti A (2014) Focus on molecular events in the anterior chamber leading to glaucoma. Cell Mol Life Sci 71:2197–2218PubMedCrossRefGoogle Scholar
  204. Saccà SC, Pascotto A, Camicione P, Capris P, Izzotti A (2005) Oxidative DNA damage in the human trabecular meshwork: clinical correlation in patients with primary open-angle glaucoma. Arch Ophthalmol 123:458–463PubMedCrossRefGoogle Scholar
  205. Saccà SC, Izzotti A, Rossi P, Traverso C (2007) Glaucomatous outflow pathway and oxidative stress. Exp Eye Res 84:389–399PubMedCrossRefGoogle Scholar
  206. Saccà SC, Bolognesi C, Battistella A, Bagnis A, Izzotti A (2009) Gene-environment interactions in ocular diseases. Mutat Res 667:98–117Google Scholar
  207. Saccà SC, Centofanti M, Izzotti A (2012) New proteins as vascular biomarkers in primary open angle glaucomatous aqueous humor. Invest Ophthalmol Vis Sci 53:4242–4253Google Scholar
  208. Saccà SC, Roszkowska AM, Izzotti A (2013) Environmental light and endogenous antioxidants as the main determinants of non-cancer ocular diseases. Mutat Res 752:153–171PubMedCrossRefGoogle Scholar
  209. Saccà SC, Pulliero A, Izzotti A (2015) The dysfunction of the trabecular meshwork during glaucoma course. J Cell Physiol 230:510–525PubMedCrossRefGoogle Scholar
  210. Saccà SC, Gandolfi S, Bagnis A, Manni G, Damonte G et al (2016a) From DNA damage to functional changes of the trabecular meshwork in ageing and glaucoma. Ageing Res Rev 29:26–41Google Scholar
  211. Saccà SC, Gandolfi S, Bagnis A, Manni G, Damonte G et al (2016b) The outflow pathway: a tissue with morphological and functional unity. J Cell Physiol 231:1876–1893PubMedCrossRefGoogle Scholar
  212. Saitoh T, Akira S (2010) Regulation of innate immune responses by autophagy-related proteins. J Cell Biol 189:925–935PubMedPubMedCentralCrossRefGoogle Scholar
  213. Salminen A, Ojala J, Kaarniranta K, Haapasalo A, Hiltunen M et al (2011) Astrocytes in the ageing brain express characteristics of senescence-associated secretory phenotype. Eur J Neurosci 34:3–11PubMedCrossRefGoogle Scholar
  214. Sampaio TB, Savall AS, Gutierrez MEZ, Pinton S (2017) Neurotrophic factors in Alzheimer’s and Parkinson’s diseases: implications for pathogenesis and therapy. Neural Regen Res 12:549–557PubMedPubMedCentralCrossRefGoogle Scholar
  215. Sanderson JL, Dell’Acqua ML (2011) AKAP signaling complexes in regulation of excitatory synaptic plasticity. Neuroscientist 17:321–336PubMedPubMedCentralCrossRefGoogle Scholar
  216. Sanderson J, Dartt DA, Trinkaus-Randall V, Pintor J, Civan MM et al (2014) Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland. Exp Eye Res 127:270–279PubMedCrossRefGoogle Scholar
  217. Sawada H, Fukuchi T, Tanaka T, Abe H (2010) Tumor necrosis factor-alpha concentrations in the aqueous humor of patients with glaucoma. Invest Ophthalmol Vis Sci 51:903–906PubMedCrossRefGoogle Scholar
  218. Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ et al (1998) Two CD95 (APO-1/Fas) signaling pathways. EMBO J 17:1675–1687PubMedPubMedCentralCrossRefGoogle Scholar
  219. Scott JD (1991) Cyclic nucleotide-dependent protein kinases. Pharmacol Ther 50:123–145PubMedCrossRefGoogle Scholar
  220. Scott JD (2003) A-kinase-anchoring proteins and cytoskeletal signalling events. Biochem Soc Trans 31:87–89PubMedCrossRefGoogle Scholar
  221. Sejersen T, Lendahl U (1993) Transient expression of the intermediate filament nestin during skeletal muscle development. J Cell Sci 106(Pt 4):1291–1300PubMedGoogle Scholar
  222. Sekiguchi F, Aoki Y, Nakagawa M, Kanaoka D, Nishimoto Y et al (2013) AKAP-dependent sensitization of Ca(v) 3.2 channels via the EP(4) receptor/cAMP pathway mediates PGE(2) -induced mechanical hyperalgesia. Br J Pharmacol 168:734–745PubMedPubMedCentralCrossRefGoogle Scholar
  223. Shen X, Koga T, Park BC, SundarRaj N, Yue BY (2008) Rho GTPase and cAMP/protein kinase A signaling mediates myocilin-induced alterations in cultured human trabecular meshwork cells. J Biol Chem 283:603–612PubMedCrossRefGoogle Scholar
  224. Shen X, Ying H, Qiu Y, Park JS, Shyam R et al (2011) Processing of optineurin in neuronal cells. J Biol Chem 286:3618–3629PubMedCrossRefGoogle Scholar
  225. Shiga N, Hirano K, Hirano M, Nishimura J, Nawata H et al (2005) Long-term inhibition of RhoA attenuates vascular contractility by enhancing endothelial NO production in an intact rabbit mesenteric artery. Circ Res 96:1014–1021PubMedCrossRefGoogle Scholar
  226. Shigenaga MK, Hagen TM, Ames BN (1994) Oxidative damage and mitochondrial decay in ageing. Proc Natl Acad Sci U S A 91:10771–10778PubMedPubMedCentralCrossRefGoogle Scholar
  227. Shimizu S, Lichter PR, Johnson AT, Zhou Z, Higashi M et al (2000) Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle glaucoma. Am J Ophthalmol 130:165–177PubMedCrossRefGoogle Scholar
  228. Shimizu T, Sugawara K, Tosaka M, Imai H, Hoya K et al (2006) Nestin expression in vascular malformations: a novel marker for proliferative endothelium. Neurol Med Chir (Tokyo) 46:111–117CrossRefGoogle Scholar
  229. Smith PJ, Samuelson DA, Brooks DE, Whitley RD (1986) Unconventional aqueous humour outflow of microspheres perfused into the equine eye. Am J Vet Res 47:2445–2453PubMedGoogle Scholar
  230. Smith ND, Crabb DP, Garway-Heath DF (2011) An exploratory study of visual search performance in glaucoma. Ophthalmic Physiol Opt 31:225–232PubMedCrossRefGoogle Scholar
  231. Smythe E, Ayscough KR (2006) Actin regulation in endocytosis. J Cell Sci 119:4589–4598PubMedCrossRefGoogle Scholar
  232. Soto D, Comes N, Ferrer E, Morales M, Escalada A et al (2004) Modulation of aqueous humor outflow by ionic mechanisms involved in trabecular meshwork cell volume regulation. Invest Ophthalmol Vis Sci 45:3650–3661PubMedCrossRefGoogle Scholar
  233. Spector A (1995) Oxidative stress-induced cataract: mechanism of action. FASEB J 9:1173–1182PubMedCrossRefGoogle Scholar
  234. Sriram K, O’Callaghan JP (2007) Divergent roles for tumor necrosis factor-alpha in the brain. J Neuroimmune Pharmacol 2:140–153PubMedCrossRefGoogle Scholar
  235. Steely HT Jr, English-Wright SL, Clark AF (2000) The similarity of protein expression in trabecular meshwork and lamina cribrosa: implications for glaucoma. Exp Eye Res 70:17–30PubMedCrossRefGoogle Scholar
  236. Stone EM, Fingert JH, Alward WL, Nguyen TD, Polansky JR et al (1997) Identification of a gene that causes primary open angle glaucoma. Science 275:668–670PubMedCrossRefGoogle Scholar
  237. Stothert AR, Fontaine SN, Sabbagh JJ, Dickey CA (2016) Targeting the ER-autophagy system in the trabecular meshwork to treat glaucoma. Exp Eye Res 144:38e45CrossRefGoogle Scholar
  238. Sun H, Wang Y, Pang IH, Shen J, Tang X et al (2011) Protective effect of a JNK inhibitor against retinal ganglion cell loss induced by acute moderate ocular hypertension. Mol Vis 17:864–875PubMedPubMedCentralGoogle Scholar
  239. Surmeier DJ, Schumacker PT, Guzman JD, Ilijic E, Yang B et al (2016) Calcium and Parkinson’s disease. Biochem Biophys Res Commun 483:1013–1019PubMedPubMedCentralCrossRefGoogle Scholar
  240. Suzuki S, Namiki J, Shibata S, Mastuzaki Y, Okano H (2010) The neural stem/progenitor cell marker nestin is expressed in proliferative endothelial cells, but not in mature vasculature. J Histochem Cytochem 58:721–730PubMedPubMedCentralCrossRefGoogle Scholar
  241. Tamm ER (2002) Myocilin and glaucoma: facts and ideas. Prog Retin Eye Res 21:395–428PubMedCrossRefGoogle Scholar
  242. Tamm ER (2009) The trabecular meshwork outflow pathways: structural and functional aspects. Exp Eye Res 88:648–655Google Scholar
  243. Teranishi N, Naito Z, Ishiwata T, Tanaka N, Furukawa K et al (2002) Identification of neovasculature using nestin in colorectal cancer. Int J Oncol 30:593–603Google Scholar
  244. Tezel G (2008) TNF-alpha signaling in glaucomatous neurodegeneration. Prog Brain Res 173:409–421PubMedPubMedCentralCrossRefGoogle Scholar
  245. Tezel G, Chauhan BC, LeBlanc RP, Wax MB (2003) Immunohistochemical assessment of the glial mitogen-activated protein kinase activation in glaucoma. Invest Ophthalmol Vis Sci 44:3025–3033PubMedCrossRefGoogle Scholar
  246. Tian B, Geiger B, Epstein DL, Kaufman PL (2000) Cytoskeletal involvement in the regulation of aqueous humor outflow. Invest Ophthalmol Vis Sci 41:619–623PubMedGoogle Scholar
  247. Toescu EC (2005) Normal brain ageing: models and mechanisms. Philos Trans R Soc Lond Ser B Biol Sci 360:2347–2354CrossRefGoogle Scholar
  248. Toescu EC, Verkhratsky A (2000) Parameters of calcium homeostasis in normal neuronal ageing. J Anat 197(pt 4):563–569PubMedPubMedCentralCrossRefGoogle Scholar
  249. Tooze SA, Schiavo G (2008) Liaisons dangereuses: autophagy, neuronal survival and neurodegeneration. Curr Opin Neurobiol 18:504–515PubMedCrossRefGoogle Scholar
  250. Toussaint O, Dumont P, Remacle J, Dierick JF, Pascal T et al (2002) Stress-induced premature senescence or stress-induced senescence-like phenotype: one in vivo reality, two possible definitions? Sci World J 2:230–247CrossRefGoogle Scholar
  251. Tsai DC, Hsu WM, Chou CK, Chen SJ, Peng CH et al (2002) Significant variation of the elevated nitric oxide levels in aqueous humor from patients with different types of glaucoma. Ophthalmologica 216:346–350PubMedCrossRefGoogle Scholar
  252. Ueno U, Yamada Y, Watanabe R, Mukai E, Hosokawa M et al (2005) Nestin-positive cells in adult pancreas express amylase and endocrine precursor cells. Pancreas 31:126–131PubMedCrossRefGoogle Scholar
  253. Ullian EM, Barkis WB, Chen S, Diamond JS, Barres BA (2004) Invulnerability of retinal ganglion cells to NMDA excitotoxicity. Mol Cell Neurosci 26:544–557PubMedCrossRefGoogle Scholar
  254. Underwood JL, Murphy GM, Chen J, Franse-Carman L, Wood I et al (1999) Glucocorticoids regulate transendothelial fluid flow resistance and formation of intercellular junctions. AmJ Physiol Cell Physiol 277:C330–C342CrossRefGoogle Scholar
  255. Vaittinen S, Lukka R, Sahlgren C, Hurme T, Rantanen J et al (2001) The expression of intermediate filament protein nestin as related to vimentin and desmin in regenerating skeletal muscle. J Neuropathol Exp Neurol 60:588–597PubMedCrossRefGoogle Scholar
  256. Valamanesh F, Monnin J, Morand-Villeneuve N, Michel G, Zaher M et al (2013) Nestin expression in the retina of rats with inherited retinal degeneration. Exp Eye Res 110C:26–34CrossRefGoogle Scholar
  257. Valentijn SA, van Boxtel MP, van Hooren SA, Bosma H, Beckers HJ et al (2005) Change in sensory functioning predicts change in cognitive functioning: results from a 6-year follow-up in the maastricht ageing study. J Am Geriatr Soc 53:374–380PubMedCrossRefGoogle Scholar
  258. Van Aelst L, D’Souza-Schorey C (1997) Rho GTPases and signaling networks. Genes Dev 11:2295–2322PubMedCrossRefGoogle Scholar
  259. Vittow J, Borras T (2002) Expression of optineurin, a glaucoma-linked gene, is influenced by elevated intraocular pressure. Biochem Biophys Res Commun 298:67–74CrossRefGoogle Scholar
  260. von Zglinicki T, Saretzki G, Ladhoff J, d’Adda di Fagagna F, Jackson SP (2005) Human cell senescence as a DNA damage response. Mech Ageing Dev 126:111–117CrossRefGoogle Scholar
  261. Walker RJ, Anderson NM, Bahouth S, Steinle JJ (2012) Silencing of insulin receptor substrate-1 increases cell death in retinal Müller cells. Mol Vis 18:271–279PubMedPubMedCentralGoogle Scholar
  262. Wang K, Klionsky DJ (2011) Mitochondria removal by autophagy. Autophagy 7:297e300Google Scholar
  263. Wang X, Tay SS, Ng YK (2000) An immunohistochemical study of neuronal and glial cell reactions in retinae of rats with experimental glaucoma. Exp Brain Res 132:476–484PubMedCrossRefGoogle Scholar
  264. Wang L, Sunahara RK, Krumins A, Perkins G, Crochiere ML et al (2001) Cloning and mitochondrial localization of full-length D-AKAP2, a protein kinase A anchoring protein. Proc Natl Acad Sci U S A 98:3220–3225PubMedPubMedCentralCrossRefGoogle Scholar
  265. Wang L, Cano M, Handa JT (2014) p62 provides dual cytoprotection against oxidative stress in the retinal pigment epithelium. Biochim Biophys Acta 1843:1248e1258Google Scholar
  266. Watkins JC, Davies J, Evans RH, Francis AA, Jones AW (1981) Pharmacology of receptors for excitatory amino acids. Adv Biochem Psychopharmacol 27:263–273PubMedGoogle Scholar
  267. Wegner AM, Nebhan CA, Hu L, Majumdar D, Meier KM, Weaver AM, Webb DJ (2008) N-wasp and the arp2/3 complex are critical regulators of actin in the development of dendritic spines and synapses. J Biol Chem 283:15912–15920PubMedPubMedCentralCrossRefGoogle Scholar
  268. Wei H, Sawchyn AK, Myers JS, Katz LJ, Moster MR et al (2012) A clinical method to assess the effect of visual loss on the ability to perform activities of daily living. Br J Ophthalmol 96:735–741PubMedCrossRefGoogle Scholar
  269. Welch MD, DePace AH, Verma S, Iwamatsu A, Mitchison TJ (1997) The human Arp2/3 complex is composed of evolutionarily conserved subunits and is localized to cellular regions of dynamic actin filament assembly. J Cell Biol 138:375–384PubMedPubMedCentralCrossRefGoogle Scholar
  270. Wentz-Hunter K, Shen X, Okazaki K, Tanihara H, Yue BY (2004) Overexpression of myocilin in cultured human trabecular meshwork cells. Exp Cell Res 297:39–48PubMedCrossRefGoogle Scholar
  271. White MF, Maron R, Kahn CR (1985) Insulin rapidly stimulates tyrosine phosphorylation of a Mr-185,000 protein in intact cells. Nat (Lond) 318:183–186CrossRefGoogle Scholar
  272. Wiederholt M (1998) Direct involvement of trabecular meshwork in the regulation of aqueous humor outflow. Curr Opin Ophthalmol 9:46–49PubMedCrossRefGoogle Scholar
  273. Wiederholt M, Thieme H, Stumpff F (2000) The regulation of trabecular meshwork and ciliary muscle contractility. Prog Retin Eye Res 19:271–295PubMedCrossRefGoogle Scholar
  274. Xu J, Pokorny J, Smith VC (1997) Optical density of the human lens. J Opt Soc Am A Opt Image Sci Vis 14:953–960PubMedCrossRefGoogle Scholar
  275. Xue LP, Lu J, Cao Q, Hu S, Ding P et al (2006) Müller glial cells express nestin coupled with glial fibrillary acidic protein in experimentally induced glaucoma in the rat retina. Neuroscience 139:723–732PubMedCrossRefGoogle Scholar
  276. Yang HY, Lieska N, Kriho V, Wu CM, Pappas GD (1997) Subpopulation of reactive astrocytes at the immediate site of cerebral cortical injury. Exp Neuol 146:199–205CrossRefGoogle Scholar
  277. Ye W, Gong H, Sit A, Johnson M, Freddo TF (1997) Interendothelial junctions in normal human Schlemm’s canal respond to changes in pressure. Invest Ophthalmol Vis Sci 38:2460–2468PubMedGoogle Scholar
  278. Ying H, Yue BYT (2016) Optineurin: the autophagy connection. Exp Eye Res 144:73–80PubMedCrossRefGoogle Scholar
  279. Zetterberg M (2016) Age-related eye disease and gender. Maturitas 83:19–26PubMedCrossRefGoogle Scholar
  280. Zgheib O, Huyen Y, DiTullio RA Jr, Snyder A, Venere M et al (2005) ATM signaling and 53BP1. Radiother Oncol 76:119–122PubMedCrossRefGoogle Scholar
  281. Zhang J, Shapiro MS (2012) Activity-dependent transcriptional regulation of M-Type (Kv7) K(+) channels by AKAP79/150-mediated NFAT actions. Neuron 76:1133–1146PubMedPubMedCentralCrossRefGoogle Scholar
  282. Zhang M, Maddala R, Rao PV (2008) Novel molecular insights into RhoA GTPase-induced resistance to aqueous humor outflow through the trabecular meshwork. Am J Physiol Cell Physiol 295:C1057–C1070PubMedPubMedCentralCrossRefGoogle Scholar
  283. Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature 469:221–225PubMedCrossRefGoogle Scholar
  284. Zhu G, Lee AS (2014) Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis. J Cell Physiol 230:1413e1420Google Scholar
  285. Zinflou C, Rochette PJ (2017) Ultraviolet A-induced oxidation in cornea: characterization of the early oxidation-related events. Free Radic Biol Med 108:118–128PubMedCrossRefGoogle Scholar
  286. Zuchero JB, Belin B, Mullins RD (2012) Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY. Mol Biol Cell 23:853–863PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Sergio Claudio Saccà
    • 1
    Email author
  • Carlo Alberto Cutolo
    • 2
  • Tommaso Rossi
    • 1
  1. 1.Department of Head/Neck PathologiesSt Martino Hospital, Ophthalmology UnitGenoaItaly
  2. 2.Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child ScienceUniversity of Genoa, Policlinico San Martino Hospital, Eye Clinic GenoaGenoaItaly

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