Advertisement

Resveratrol Protects Optic Nerve Head Astrocytes from Oxidative Stress-Induced Cell Death by Preventing Caspase-3 Activation, Tau Dephosphorylation at Ser422 and Formation of Misfolded Protein Aggregates

  • John C. Means
  • Adam A. Lopez
  • Peter KoulenEmail author
Original Research
  • 41 Downloads

Abstract

Optic nerve head astrocytes (ONHAs) are the major cell type within the optic nerve head, providing both structural and nutrient support to the optic nerve. Astrocytes are necessary for the survival of neurons with controlled activation of astrocytes being beneficial to neurons. However, overactive astrocytes can be harmful and the loss of normal astrocyte function can be a primary contributor to neurodegeneration. The neuroprotective properties of reactive astrocytes can be lost or they might gain neurotoxic properties in neurodegenerative diseases. The activated astrocytes are crucial in the development of glaucoma, where they serve as a source for cytotoxic substances that participate in ganglion apoptosis. There is increasing evidence indicating that neuroinflammation is an important process in glaucoma. Under pathological conditions, astrocytes can induce an inflammatory response. Extensive evidence shows that inflammatory responses mediated by astrocytes can also influence pathology development, synapse health, and neurodegeneration. The elimination of activated astrocytes by apoptosis is also expected in unfavorable conditions. In neurodegenerative diseases, a common feature is the presence of aggregates found in astrocytes, which can disrupt astrocyte function in such a way as to be detrimental to the viability of neurons. The biological processes involved in vision loss in glaucoma are not well understood. Despite the rapid advances in our understanding of optic nerve head (ONH) structure and function, numerous potential contributions of the ONHAs to optic nerve damage remain unanswered. The present study investigated the role of ONHAs during oxidative stress in order to determine novel cell biological processes underlying glaucoma pathogenesis. ONHAs were exposed to chemically induced oxidative stress using tert-butyl hydroperoxide (tBHP) in order to model extracellular oxidative stress as it occurs in the glaucomatous retina and ONH. In order to determine the impact of an intervention approach employing potential glioprotective treatments for central nervous system tissue we pretreated cells with the polyphenolic phytostilbene and antioxidant trans-resveratrol (3,5,4′-trihydroxy-trans-stilbene). ONHAs exposed to tBHP-mediated oxidative stress displayed decreased viability and underwent apoptosis. In addition, increased levels of activated caspases, dephosphorylation of Tau protein at Ser422, an important site adjacent to the caspase cleavage site controlling Tau cleavage, caspase-mediated Tau cleavage, and cytoskeletal changes, specifically formation of neurofibrillary tangles (NFTs) were detected in ONHAs undergoing oxidative stress. When cells were pretreated with resveratrol cell viability increased along with a significant decrease in activated caspases, cleaved Tau, and NFT formation. Taken together, ONHAs appear to act similar to neurons when undergoing oxidative stress, where proteolytic cleavage of Tau by caspases leads to NFT formation. In addition, resveratrol appears to have promise as a potential protective treatment preventing ONHA dysfunction and degeneration. There is currently no cure for glaucoma or a neuro- and glioprotective treatment that directly targets the pathogenic mechanisms in the glaucomatous retina and optic nerve. The present study identified a potential mechanism underlying degeneration of astrocytes that is susceptible to pharmaco-therapeutic intervention in the eye and potentially elsewhere in the central nervous system. Identification of such mechanisms involved in glaucoma and other disorders of the eye and brain is critical to determine novel targets for effective therapies.

Keywords

Brain Central nervous system Eye Glaucoma Neurofibrillary tangles Phosphorylation Phytostilbene Retina Tau cleavage 

Abbreviations

Amyloid β–peptide

AD

Alzheimer’s disease

ANOVA

Analysis of variance

CSF

Cerebral spinal fluid

GFAP

Glial fibrillary acidic protein

NFT

Neurofibrillary tangle

ONH

Optic nerve head

ONHA

Optic nerve head astrocyte

PBS

Phosphate buffered saline

PFA

Paraformaldehyde

tBHP

Tert-butyl hydroperoxide

Notes

Acknowledgements

Research reported in this publication was supported in part by grants from the National Institutes of Health, National Eye Institute Grants EY014227 and EY022774, National Institute on Aging grant AG027956, National Center for Research Resources/National Institute of General Medical Sciences Grant RR027093 (PK) and a National Institutes of Health Clinical and Translational Science Award Grant (UL1 TR002366) awarded to the University of Kansas. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support by the Felix and Carmen Sabates Missouri Endowed Chair in Vision Research and a Challenge Grant from Research to Prevent Blindness (PK) is gratefully acknowledged.

Author contributions

JCM and PK conceived and designed the experiments; JCM, AAL and PK performed the experiments; JCM, AAL, and PK analyzed the data and wrote the paper. All authors read and approved the final manuscript.

Funding

Research reported in this publication was supported in part by grants from the National Institutes of Health, National Eye Institute grants EY014227 and EY022774, National Institute on Aging Grant AG027956, National Center for Research Resources/National Institute of General Medical Sciences grant RR027093 (PK) and a National Institutes of Health Clinical and Translational Science Award Grant (UL1 TR002366) awarded to the University of Kansas. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support by the Felix and Carmen Sabates Missouri Endowed Chair in Vision Research and a Challenge Grant from Research to Prevent Blindness (PK) is gratefully acknowledged.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

Not applicable.

Supplementary material

10571_2019_781_MOESM1_ESM.docx (832 kb)
Electronic supplementary material 1 (DOCX 832 kb)

References

  1. Abramov AY, Canevari L, Duchen MR (2003) Changes in intracellular calcium and glutathione in astrocytes as the primary mechanism of amyloid neurotoxicity. J Neurosci 23:5088–5095PubMedPubMedCentralCrossRefGoogle Scholar
  2. Abu-Amero KK, Kondkar AA, Chalam KV (2016) Resveratrol and ophthalmic diseases. Nutrients 8(4):200.  https://doi.org/10.3390/nu8040200 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Al-Kharashi AS (2018) Role of oxidative stress, inflammation, hypoxia and angiogenesis in the development of diabetic retinopathy. Saudi J Ophthalmol 32(4):318–323PubMedPubMedCentralCrossRefGoogle Scholar
  4. Allaman I, Gavillet M, Belanger M, Laroche T, Viertl D, Lashuel HA, Magistretti PJ (2010) Amyloid-β aggregates cause alterations of astrocytic metabolic phenotype: Impact on neuronal viability. J Neurosci 30:3326–3338PubMedPubMedCentralCrossRefGoogle Scholar
  5. Andrae J, Bongcam-Rudloff E, Hansson I, Lendahl U, Westermark B, Nister M (2001) A 1.8kb GFAP-promoter fragment is active in specific regions of the embryonic CNS. Mech Dev 107(1–2):181–185Google Scholar
  6. Araque A, Navarrete M (2010) Glial cells in neuronal network function. Philos Trans R Soc Lond B Biol Sci 365(1551):2375–2381PubMedPubMedCentralCrossRefGoogle Scholar
  7. Armstrong RA (2010) Alzheimer's disease and the eye. J Optometry 2(3):103–111CrossRefGoogle Scholar
  8. Beach TG, Walker R, McGeer EG (1989) Patterns of gliosis in Alzheimer’s disease and aging cerebrum. Glia 2(6):420–436PubMedCrossRefPubMedCentralGoogle Scholar
  9. Beal MF (1995) Aging, energy, and oxidative stress in neurodegenerative diseases. Ann Neurol 38:357–366PubMedCrossRefPubMedCentralGoogle Scholar
  10. Bélanger M, Magistretti PJ (2009) The role of astroglia in neuroprotection. Dialogues Clin Neurosci 11:281–295PubMedPubMedCentralGoogle Scholar
  11. Bellaver B, Souza DG, Souza DO, Quincozes-Santos A (2016) Hippocampal astrocyte cultures from adult and aged rats reproduce changes in glial functionality observed in the aging brain. Mol Neurobiol 54(4):2969–2985PubMedCrossRefPubMedCentralGoogle Scholar
  12. Bellaver B, Souza DG, Souza DO, Quincozes-Santos A (2017) Hippocampal astrocyte cultures from adult and aged rats reproduce changes in glial functionality observed in the aging brain. Mol Neurobiol 54(4):2969–2985PubMedCrossRefPubMedCentralGoogle Scholar
  13. Bhullar KS (1852) Hubbard BP (2015) Lifespan and healthspan extension by resveratrol. Biochim Biophys Acta 6:1209–1218Google Scholar
  14. Blennow K (2004) Cerebrospinal fluid protein biomarkers for Alzheimer's disease. NeuroTher 1(2):213–225CrossRefGoogle Scholar
  15. Brahmachari S, Fung YK, Pahan K (2006) Induction of glial fibrillary acidic protein expression in astrocytes by nitric oxide. J Neurosci 26(18):4930–4939PubMedPubMedCentralCrossRefGoogle Scholar
  16. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer's disease. Alzheimers Dement 3:186–219PubMedCrossRefPubMedCentralGoogle Scholar
  17. Carter LG, D'Orazio JA, Pearson KJ (2014) Resveratrol and cancer: focus on in vivo evidence. Endocr Relat Cancer 21(3):R209–R225PubMedPubMedCentralCrossRefGoogle Scholar
  18. Cesareo M, Martucci A, Ciuffoletti E, Mancino R, Cerulli A, Sorge RP, Martorana A, Sancesario G, Nucci C (2015) Association between Alzheimer’s disease and glaucoma: a study based on heidelberg retinal tomography and frequency doubling technology perimetry. Front Neurosci 9:479PubMedPubMedCentralCrossRefGoogle Scholar
  19. Chen X, Guo C, Kong J (2012) Oxidative stress in neurodegenerative diseases. Neural Regen Res 7(5):376–385PubMedPubMedCentralGoogle Scholar
  20. Chesser AS, Pritchard SM, Johnson GV (2013) Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease. Front Neurol 4:122.  https://doi.org/10.3389/fneur.2013.00122 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Chiasseu M, Cueva Vargas JL, Destroismaisons L, Vande Velde C, Leclerc N, Di Polo A (2016) Tau accumulation, altered phosphorylation, and missorting promote neurodegeneration in glaucoma. J Neurosci 36(21):5785–5798PubMedPubMedCentralCrossRefGoogle Scholar
  22. Chiasseu M, Alarcon-Martinez L, Belforte N, Quintero H, Dotigny F, Destroismaisons L, Vande Velde C, Panayi F, Louis C, Di Polo A (2017) Tau accumulation in the retina promotes early neuronal dysfunction and precedes brain pathology in a mouse model of Alzheimer's disease. Mol Neurodegener 12(1):58.  https://doi.org/10.1186/s13024-017-0199-3 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Chong RS, Martin KR (2015) Glial cell interactions and glaucoma. Curr Opin Ophthalmol 26(2):73–77PubMedPubMedCentralCrossRefGoogle Scholar
  24. Chun H, Marriott I, Lee CJ, Cho H (2018) Elucidating the interactive roles of glia in alzheimer's disease using established and newly developed experimental models. Front Neurol 9:797PubMedPubMedCentralCrossRefGoogle Scholar
  25. Clarke LE, Liddelow SA, Chakraborty C, Münch AE, Heiman M, Barres BA (2018) Normal aging induces A1-like astrocyte reactivity. Proc Natl Acad Sci USA 115(8):E1896–E2190PubMedCrossRefPubMedCentralGoogle Scholar
  26. Colodner KJ, Feany MB (2010) Glial fibrillary tangles and JAK/STAT-mediated glial and neuronal cell death in a drosophila model of glial tauopathy. J Neurosci 30:16102–16111PubMedPubMedCentralCrossRefGoogle Scholar
  27. Corvetti L, Aztiria E, Domenici L (2006) Reduction of GFAP induced by long dark rearing is not restricted to visual cortex. Brain Res 1067(1):146–153PubMedCrossRefPubMedCentralGoogle Scholar
  28. Cotman C, Poon W, Rissman R, Blurton-Jones M (2005) The role of caspase cleavage of tau in Alzheimer disease neuropathology. J Neuropathol Exp Neurol 64:104–112PubMedCrossRefPubMedCentralGoogle Scholar
  29. Cotrina ML, Nedergaard M (2002) Astrocytes in the aging brain. J Neurosci Res 67(1):1–10PubMedCrossRefPubMedCentralGoogle Scholar
  30. Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262:689–695PubMedCrossRefPubMedCentralGoogle Scholar
  31. Cucciolla V, Borriello A, Oliva A, Galletti P, Zappia V, Della F (2007) Resveratrol: from basic science to the clinic. Cell Cycle 6(20):2495–2510PubMedCrossRefGoogle Scholar
  32. D’Qmelio M, Sheng M, Cecconi F (2012) Caspase-3 in the central nervous system: beyond apoptosis. Trends Neurosci 35(11):700–709CrossRefGoogle Scholar
  33. Dabir DV, Robinson MB, Swanson E, Zhang B, Trojanowski JQ, Lee VM, Forman MS (2006) Impaired glutamate transport in a mouse model of tau pathology in astrocytes. J Neurosci 26(2):644–654PubMedPubMedCentralCrossRefGoogle Scholar
  34. Dai C, Khaw PT, Yin ZQ, Li D, Raisman G, Li Y (2012) Structural basis of glaucoma: the fortified astrocytes of the optic nerve head are the target of raised intraocular pressure. Glia 60(1):13–28PubMedCrossRefGoogle Scholar
  35. de Hoz R, Rojas B, Ramírez AI, Salazar JJ, Gallego BI, Triviño A, Ramírez JM (2016) Retinal macroglial responses in health and disease. Biomed Res Int 2016:2954721PubMedPubMedCentralGoogle Scholar
  36. de Sá Coutinho D, Pacheco MT, Frozza RL, Bernardi A (2018) Anti-inflammatory effects of resveratrol: mechanistic insights. Int J Mol Sci 19(6):1812Google Scholar
  37. de la Lastra CA, Villegas I (2007) Resveratrol as an antioxidant and prooxidant agent: mechanisms and clinical implications. Biochem Soc Trans 35(Pt 5):1156–1160PubMedGoogle Scholar
  38. Dossi E, Vasile F, Rouach N (2018) Human astrocytes in the diseased brain. Brain Res Bull 136:139–156PubMedPubMedCentralCrossRefGoogle Scholar
  39. Duncan AJ, Heales SJ (2005) Nitric oxide and neurological disorders. Mol Aspects Medv 26:67–96CrossRefGoogle Scholar
  40. Eng LF, Ghirnikar RS (1994) GFAP and astrogliosis. Brain Pathol 4:229–237PubMedCrossRefPubMedCentralGoogle Scholar
  41. Eng LF, Yu AC, Lee YL (1992) Astrocytic response to injury. Prog Brain Res 94:353–365PubMedCrossRefPubMedCentralGoogle Scholar
  42. Feany MB, Dickson DW (1995) Widespread cytoskeletal pathology characterizes corticobasal degeneration. Am J Pathol 146:1388–1396PubMedPubMedCentralGoogle Scholar
  43. Feng Z, Zhang JT (2004) Protective effect of melatonin on beta-amyloid-induced apoptosis in rat astroglioma C6 cells and its mechanism. Free Radic Biol Med 37:1790–1801PubMedCrossRefPubMedCentralGoogle Scholar
  44. Ferreira SM, Lerner SF, Brunzini R, Evelson PA, Llesuy SF (2004) Oxidative stress markers in aqueous humor of glaucoma patients. Am J Ophthalmol 137(1):62–69PubMedCrossRefPubMedCentralGoogle Scholar
  45. Ferrer I, Blanco R (2000) N-myc and c-myc expression in Alzheimer disease, Huntington disease and Parkinson disease. Brain Res Mol Brain Res 77:270–276PubMedCrossRefPubMedCentralGoogle Scholar
  46. Ferrer I, Blanco R, Carmona M, Ribera R, Goutan E, Puig B, Rey MJ, Cardozo A, Vinals F, Ribalta T (2001) Phosphorylated map kinase (ERK1, ERK2) expression is associated with early tau deposition in neurones and glial cells, but not with increased nuclear DNA vulnerability and cell death, in Alzheimer disease, Pick’s disease, progressive supranuclear palsy and corticobasal degeneration. Brain Pathol 11:144–158PubMedCrossRefPubMedCentralGoogle Scholar
  47. Forman MS, Lal D, Zhang B, Dabir DV, Swanson E, Lee VM, Trojanowski JQ (2005a) Transgenic mouse model of tau pathology in astrocytes leading to nervous system degeneration. J Neurosci 25:3539–3550PubMedPubMedCentralCrossRefGoogle Scholar
  48. Forman M, Lal D, Zhang B, Dabir DV, Swanson E, Lee V, Trojanowski JQ (2005b) Transgenic mouse models of TAU pathology in astrocytes leading to nervous system degeneration. J Neurosci 25(14):3539–3550PubMedPubMedCentralCrossRefGoogle Scholar
  49. Frank-Cannon TC, Alto LT, McAlpine FE, Tansey MG (2009) Does neuroinflammation fan the flame in neurodegenerative diseases? Mol Neurodegener 4:47.  https://doi.org/10.1186/1750-1326-4-47 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Friedman DS, Holbrook JT, Ansari H, Alexander J, Burke A, Reed SB, Katz J, Thorne JE, Lightman SL, Kempen JH (2013) Risk of elevated intraocular pressure and glaucoma in patients with uveitis: results of the multicenter uveitis steroid treatment trial. Ophthalmology 120(8):1571–1579PubMedPubMedCentralCrossRefGoogle Scholar
  51. Frost GR, Li YM (2017) The role of astrocytes in amyloid production and Alzheimer's disease. Open Biol 7(12):170228PubMedPubMedCentralCrossRefGoogle Scholar
  52. Gallego BI, Salazar JJ, de Hoz R, Rojas B, Ramírez AI, Salinas-Navarro M, Ortín-Martínez A, Valiente-Soriano FJ, Avilés-Trigueros M, Villegas-Perez MP, Vidal-Sanz M, Triviño A, Ramírez JM (2012) IOP induces upregulation of GFAP and MHC-II and microglia reactivity in mice retina contralateral to experimental glaucoma. J Neuroinflamm 9:92.  https://doi.org/10.1186/1742-2094-9-92 CrossRefGoogle Scholar
  53. Gao YL, Wang N, Sun FR, Cao XP, Zhang W, Yu JT (2018) Tau in neurodegenerative disease. Ann Transl Med 6(10):175PubMedPubMedCentralCrossRefGoogle Scholar
  54. Garwood CJ, Pooler AM, Atherton J, Hanger DP, Noble W (2011) Astrocytes are important mediators of Aβ-induced neurotoxicity and tau phosphorylation in primary culture. Cell Death Dis 2:e167PubMedPubMedCentralCrossRefGoogle Scholar
  55. Gasparini L, Crowther RA, Martin KR, Berg N, Coleman M, Goedert M, Spillantini MG (2011) Tau inclusions in retinal ganglion cells of human P301S tau transgenic mice: effects on axonal viability. Neurobiol Aging 32(3):419–433PubMedCrossRefPubMedCentralGoogle Scholar
  56. Gendron TF, Petrucelli L (2009) The role of tau in neurodegeneration. Mol Neurodegener 4:13.  https://doi.org/10.1186/1750-1326-4-13 CrossRefPubMedPubMedCentralGoogle Scholar
  57. Giffard RG, Swanson RA (2005) Ischemia-induced programmed cell death in astrocytes. Glia 50:299–306PubMedCrossRefPubMedCentralGoogle Scholar
  58. Guo L, Salt TE, Luong V, Wood N, Cheung W, Maass A, Ferrari G, Russo-Marie F, Sillito AM, Cheetham ME, Moss SE, Fitzke FW, Cordeiro MF (2007) Targeting amyloid-beta in glaucoma treatment. Proc Natl Acad Sci USA 104(33):13444–13449PubMedCrossRefPubMedCentralGoogle Scholar
  59. Gupta N, Fong J, Ang LC, Yucel YH (2008) Retinal tau pathology in human glaucomas. Can J Ophthalmol 43(1):53–60PubMedCrossRefPubMedCentralGoogle Scholar
  60. Han G, Xia J, Gao J, Inagaki Y, Tang W, Kokudo N (2015) Anti-tumor effects and cellular mechanisms of resveratrol. Drug Discov Ther 9(1):1–12PubMedCrossRefPubMedCentralGoogle Scholar
  61. Hanzel DK, Trojanowski JQ, Johnston RF, Loring JF (1999) High-throughput quantitative histological analysis of Alzheimer’s disease pathology using a confocal digital microscanner. Nat Biotechnol 17(1):53–57PubMedCrossRefPubMedCentralGoogle Scholar
  62. Hernandez MR (2000) The optic nerve head in glaucoma: role of astrocytes in tissue remodeling. Prog Retin Eye Res 19:297–321PubMedCrossRefPubMedCentralGoogle Scholar
  63. Hernandez MR, Pena JD, Selvidge JA, Salvador-Silva M, Yang P (2000) Hydrostatic pressure stimulates synthesis of elastin in cultured optic nerve head astrocytes. Glia 32(2):122–136PubMedCrossRefPubMedCentralGoogle Scholar
  64. Hernandez MR, Agapova OA, Yang P, Salvador-Silva M, Ricard CS, Aoi S (2002) Differential gene expression in astrocytes from human normal and glaucomatous optic nerve head analyzed by cDNA microarray. Glia 38:45–64PubMedCrossRefPubMedCentralGoogle Scholar
  65. Hernandez MR, Miao H, Lukas T (2008) Astrocytes in glaucomatous optic neuropathy. Prog. Brain Res 173:353–373PubMedCrossRefPubMedCentralGoogle Scholar
  66. Ho WL, Leung Y, Tsang AW, So KF, Chiu K, Chang RC (2012) Review: tauopathy in the retina and optic nerve: does it shadow pathological changes in the brain? Mol Vision 18:2700–2710Google Scholar
  67. Howell GR, Soto I, Zhu X, Ryan M, Macalinao DG, Sousa GL, Caddle LB, MacNicoll KH, Barbay JM, Porciatti V, Anderson MG, Smith RS, Clark AF, Libby RT, John SW (2012) Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma. J Clin Investig 122(4):1246–1261PubMedCrossRefPubMedCentralGoogle Scholar
  68. Hurst WJ, Glinski JA, Miller KB, Apgar J, Davey MH, Stuart DA (2008) Survey of the trans-resveratrol and trans-piceid content of cocoa-containing and chocolate products. J Agric Food Chem 56(18):8374–8378PubMedCrossRefPubMedCentralGoogle Scholar
  69. Jana K, Banerjee B, Parida PK (2013) Caspases: a potential therapeutic targets in the treatment of Alzheimer’s disease. Transl Med.  https://doi.org/10.4172/2161-1025:S2-00 CrossRefGoogle Scholar
  70. Javaid FZ, Brenton J, Guo L, Cordeiro MF (2016) Visual and ocular manifestations of Alzheimer's disease and their use as biomarkers for diagnosis and progression. Front Neurol 7:55.  https://doi.org/10.3389/fneur.2016.00055 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Jeandet P, Bessis R, Maume BF, Meunier P, Peyron D, Trollat P (1995) Effect of enological practices on the resveratrol isomer content of wine. J Agric Food Chem 43:316–319CrossRefGoogle Scholar
  72. Jenner P (1991) Oxidative stress as a cause of Parkinson’s disease. Acta Neurol Scand Suppl 136:6–15PubMedCrossRefPubMedCentralGoogle Scholar
  73. Jiang T, Cadenas E (2014) Astrocytic metabolic and inflammatory changes as a function of age. Aging Cell 13(6):1059–1067PubMedPubMedCentralCrossRefGoogle Scholar
  74. Jindal V (2013) Glaucoma: an extension of various chronic neurodegenerative disorders. Mol Neurobiol 48(1):186–189PubMedCrossRefPubMedCentralGoogle Scholar
  75. Jones-Odeh E, Hammond CJ (2015) How strong is the relationship between glaucoma, the retinal nerve fibre layer, and neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis? Eye (London, England) 29(10):1270–1284CrossRefGoogle Scholar
  76. Ju W, Kim K, Noh Y, Hoshijima M, Lukas T, Ellisman M, Weinreb R, Perkins G (2015) Increased mitochondrial fission and volume density by blocking glutamate excitotoxicity protect glaucomatous optic nerve head astrocytes. Glia 63(5):736–753PubMedCrossRefPubMedCentralGoogle Scholar
  77. Kahlson MA, Colodner KJ (2015) Glial tau pathology in Tauopathies: functional consequences. J Exp Neurosci 9:43–50PubMedPubMedCentralGoogle Scholar
  78. Kaja S, Payne AJ, Naumchuk Y, Levy D, Zaidi DH, Altman AM, Nawazish S, Ghuman JK, Gerdes BC, Moore MA, Koulen P (2015) Plate reader-based cell viability assays for glioprotection using primary rat optic nerve head astrocytes. Exp Eye Res 138:159–166PubMedPubMedCentralCrossRefGoogle Scholar
  79. Katz B, Rimmer S (1989) Ophthalmologic manifestations of Alzheimer’s disease. Surv Ophthalmol 34:31–43PubMedCrossRefPubMedCentralGoogle Scholar
  80. Kneynsberg A, Combs B, Christensen K, Morfini G, Kanaan NM (2017) Axonal degeneration in tauopathies: disease relevance and underlying mechanisms. Front Neurosci 11:572PubMedPubMedCentralCrossRefGoogle Scholar
  81. Ko JH, Sethi G, Um JY, Shanmugam MK, Arfuso F, Kumar AP, Bishayee A, Ahn KS (2017) The role of resveratrol in cancer therapy. Int J Mol Sci 18(12):2589PubMedCentralCrossRefGoogle Scholar
  82. Kobayashi K, Hayashi M, Nakano H, Fukutani Y, Sasaki K, Shimazaki M, Koshino Y (2002) Apoptosis of astrocytes with enhanced lysosomal activity and oligodendrocytes in white matter lesions in Alzheimer's disease. Neuropathol Appl Neurobiol 28(3):238–251PubMedCrossRefPubMedCentralGoogle Scholar
  83. Kobayashi K, Hayashi M, Nakano H, Shimazaki M, Sugimori K, Koshino Y (2004) Correlation between astrocyte apoptosis and Alzheimer changes in gray matter lesions in Alzheimer's disease. J Alzheimer's Dis 6(6):623–632CrossRefGoogle Scholar
  84. Komori T (1999) Tau-positive glial inclusions in progressive supranuclear palsy, corticobasal degeneration and Pick's disease. Brain Pathol 9:663–679PubMedCrossRefPubMedCentralGoogle Scholar
  85. Kuchibhotla KV, Lattarulo CR, Hyman BT, Bacskai BJ (2009) Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice. Science 323:1211–1215PubMedPubMedCentralCrossRefGoogle Scholar
  86. Lançon A, Frazzi R, Latruffe N (2016) Anti-oxidant, anti-inflammatory and anti-angiogenic properties of resveratrol in ocular diseases. Molecules 21(3):304PubMedPubMedCentralCrossRefGoogle Scholar
  87. Leyns CEG, Holtzman DM (2017a) Glial contributions to neurodegeneration in tauopathies. Mol Neurodegener 12(1):50PubMedPubMedCentralCrossRefGoogle Scholar
  88. Leyns C, Holtzman DM (2017b) Glial contributions to neurodegeneration in tauopathies. Mol Neurodegener 12(1):50PubMedPubMedCentralCrossRefGoogle Scholar
  89. Li H, Förstermann U (2009) Resveratrol: a multifunctional compound improving endothelial function. Editorial to: "Resveratrol supplementation gender independently improves endothelial reactivity and suppresses superoxide production in healthy rats" by S. Soylemez et al. Cardiovasc Drugs Ther 23(6):425–429PubMedPubMedCentralCrossRefGoogle Scholar
  90. Lin IC, Wang YH, Wang TJ, Wang IJ, Shen YD, Chi NF, Chien LN (2014) Glaucoma, Alzheimer's disease, and Parkinson's disease: an 8-year population-based follow-up study. PLoS ONE 9(9):e108938.  https://doi.org/10.1371/journal.pone.0108938 CrossRefPubMedPubMedCentralGoogle Scholar
  91. Liu X, Quan N (2018) Microglia and CNS interleukin-1: beyond immunological concepts. Front Neurol 9:8PubMedPubMedCentralCrossRefGoogle Scholar
  92. Liu D, Zhang L, Li Z, Zhang X, Wu Y, Yang H, Min B, Zhang X, Ma D, Lu Y (2015) Thinner changes of the retinal nerve fiber layer in patients with mild cognitive impairment and Alzheimer's disease. BMC Neurol 15:14.  https://doi.org/10.1186/s12883-015-0268-6 CrossRefPubMedPubMedCentralGoogle Scholar
  93. Lopez MS, Dempsey RJ, Vemuganti R (2015) Resveratrol neuroprotection in stroke and traumatic CNS injury. Neurochem Int 89:75–82PubMedPubMedCentralCrossRefGoogle Scholar
  94. Lyons MM, Yu C, Toma RB, Cho SY, Reiboldt W, Lee J, van Breemen RB (2003) Resveratrol in raw and baked blueberries and bilberries. J Agric Food Chem 51(20):5867–5870PubMedCrossRefPubMedCentralGoogle Scholar
  95. Mahal HS, Mukherjee T (2006) Scavenging of reactive oxygen radicals by resveratrol: antioxidant effect. Res Chem Intermed 32:59–71CrossRefGoogle Scholar
  96. Maragakis NJ, Rothstein JD (2006) Mechanisms of disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol 2(12):679–689PubMedCrossRefPubMedCentralGoogle Scholar
  97. Martucci A, Cesareo M, Napoli D, Sorge RP, Ricci F, Mancino R, Nucci C (2014) Evaluation of pupillary response to light in patients with glaucoma: a study using computerized pupillometry. Int Ophthalmol 34(6):1241–1247PubMedCrossRefPubMedCentralGoogle Scholar
  98. Matsukawa N, Yasuhara T, Hara K, Xu L, Maki M, Yu G, Kaneko Y, Ojika K, Hess DC, Borlongan CV (2009) Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke. BMC Neurosci 10:126.  https://doi.org/10.1186/1471-2202-10-126 CrossRefPubMedPubMedCentralGoogle Scholar
  99. Mattson MP, Magnus T (2006) Ageing and neuronal vulnerability. Nat Rev Neurosci 7:278–294PubMedPubMedCentralCrossRefGoogle Scholar
  100. Means JC, Gerdes BC, Koulen P (2017) Distinct mechanisms underlying resveratrol-mediated protection from types of cellular stress in C6 glioma cells. Int J Mol Sci 18(7):1521.  https://doi.org/10.3390/ijms18071521 CrossRefPubMedCentralGoogle Scholar
  101. Mietelska-Porowska A, Wasik U, Goras M, Filipek A, Niewiadomska G (2014) Tau protein modifications and interactions: their role in function and dysfunction. Int J Mol Sci 15(3):4671–4713PubMedPubMedCentralCrossRefGoogle Scholar
  102. Mohidul Hasan M, Cha M, Bajpai VK, Baek KH (2013) Production of a major stilbene phytoalexin, resveratrol in peanut (Arachis hypogaea) and peanut products: a mini review. Rev Environ Sci Bio/Technol 12(3):209–221CrossRefGoogle Scholar
  103. Morin C, Zini R, Albengres E, Bertelli AA, Bertelli A, Tillement JP (2003) Evidence for resveratrol-induced preservation of brain mitochondria functions after hypoxia-reoxygenation. Drugs Exp Clin Res 29:227–233PubMedPubMedCentralGoogle Scholar
  104. Muramori F, Kobayashi K, Nakamura I (1998) A quantitative study of neurofibrillary tangles, senile plaques and astrocytes in the hippocampal subdivisions and entorhinal cortex in Alzheimer's disease, normal controls and non-Alzheimer neuropsychiatric diseases. Psychiatry Clin Neurosci 52(6):593–599PubMedCrossRefPubMedCentralGoogle Scholar
  105. Nagele RG, Wegiel J, Venkataraman V, Imaki H, Wang KC, Wegiel J (2004) Contribution of glial cells to the development of amyloid plaques in Alzheimer’s disease. Neurobiol Aging 25:663–674PubMedCrossRefPubMedCentralGoogle Scholar
  106. Nahirnyj A, Livne-Bar I, Guo X, Sivak JM (2013) ROS detoxification and proinflammatory cytokines are linked by p38 MAPK signaling in a model of mature astrocyte activation. PLoS ONE 8(12):e83049PubMedPubMedCentralCrossRefGoogle Scholar
  107. Nickells RW, Howell GR, Soto I, John SW (2012) Under pressure: Cellular and molecular responses during glaucoma, a common neurodegeneration with axonopathy. Annu Rev Neurosci 35:153–179PubMedCrossRefPubMedCentralGoogle Scholar
  108. Nilson AN, English KC, Gerson JE, Barton Whittle T, Nicolas Crain C, Xue J, Sengupta U, Castillo-Carranza DL, Zhang W, Gupta P, Kayed R (2016) Tau oligomers associate with Inflammation in the brain and retina of tauopathy mice and in neurodegenerative diseases. J Alzheimer's Dis 55(3):1083–1109CrossRefGoogle Scholar
  109. Noh Y, Kim K, Shim M, Choi S, Choi S, Ellisman M, Weinreb R, Perkins G, Ju W (2013) Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes. Cell Death Dis 4(10):e820PubMedPubMedCentralCrossRefGoogle Scholar
  110. Nucci C, Martucci A, Martorana A, Sancesario GM, Cerulli L (2011) Glaucoma progression associated with altered cerebral spinal fluid levels of amyloid beta and tau proteins. Clin Exp Ophthalmol 39:279–281PubMedCrossRefPubMedCentralGoogle Scholar
  111. Nucci C, Martucci A, Cesareo M, Mancino R, Russo R, Bagetta G, Cerulli L, Garaci FG (2013) Brain involvement in glaucoma: advanced neuroimaging for understanding and monitoring a new target for therapy. Curr Opin Pharmacol 13(1):128–133PubMedCrossRefPubMedCentralGoogle Scholar
  112. Nucci C, Martucci A, Cesareo M, Garaci F, Morrone LA, Russo R, Corasaniti MT, Bagetta G, Mancino R (2015) Links among glaucoma, neurodegenerative, and vascular diseases of the central nervous system. Prog Brain Res 221:49–65PubMedCrossRefPubMedCentralGoogle Scholar
  113. Nucci C, Russo R, Martucci A, Giannini C, Garaci F, Floris R, Bagetta G, Morrone LA (2016) New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system. Eur J Pharmacol 787:119–126PubMedCrossRefPubMedCentralGoogle Scholar
  114. Oksanen M, Petersen AJ, Naumenko N, Puttonen K, Lehtonen Š, Gubert Olivé M, Shakirzyanova A, Leskelä S, Sarajärvi T, Viitanen M, Rinne JO, Hiltunen M, Haapasalo A, Giniatullin R, Tavi P, Zhang SC, Kanninen KM, Hämäläinen RH, Koistinaho J (2017) PSEN1 mutant iPSC-derived model reveals severe astrocyte pathology in Alzheimer's disease. Stem Cell Rep 9(6):1885–1897CrossRefGoogle Scholar
  115. Orre M, Kamphuis W, Osborn LM, Melief J, Kooijman L, Huitinga I, Klooster J, Bossers K, Hol EM (2014) Acute isolation and transcriptome characterization of cortical astrocytes and microglia from young and aged mice. Neurobiol Aging 35(1):1–14PubMedCrossRefPubMedCentralGoogle Scholar
  116. Paradisi S, Sacchetti B, Balduzzi M, Gaudi S, Malchiodi-Albedi F (2004a) Astrocyte modulation of in vitro beta-amyloid neurotoxicity. Glia 46:252–260PubMedCrossRefPubMedCentralGoogle Scholar
  117. Paradisi S, Sacchetti B, Balduzzi M, Gaudi S, Malchiodi-Albedi F (2004b) Astrocyte modulation of in vitro β-amyloid neurotoxicity. Glia 46:252–260PubMedCrossRefPubMedCentralGoogle Scholar
  118. Phatnani H, Maniatis T (2015) Astrocytes in neurodegenerative disease. Cold Spring Harbor Perspect Biol 7(6):a020628CrossRefGoogle Scholar
  119. Prasanna G, Krishnamoorthy R, Yorio T (2010) Endothelin, astrocytes and glaucoma. Exp Eye Res 93(2):170–177PubMedPubMedCentralCrossRefGoogle Scholar
  120. Pritchard SM, Dolan PJ, Vitkus A, Johnson GV (2011) The toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics. J Cell Mol Med 15(8):1621–1635CrossRefGoogle Scholar
  121. Quigley HA (1999) Neuronal death in glaucoma. Prog Retin Eye Res 18:39–57PubMedCrossRefPubMedCentralGoogle Scholar
  122. Quigley HA (2011) Glaucoma. Lancet 377:1367–1377PubMedCrossRefPubMedCentralGoogle Scholar
  123. Quinn JP, Corbett NJ, Kellett K, Hooper NM (2018) Tau proteolysis in the pathogenesis of tauopathies: neurotoxic fragments and novel biomarkers. J Alzheimer's Dis 63(1):13–33CrossRefGoogle Scholar
  124. Ramirez AI, de Hoz R, Salobrar-Garcia E, Salazar JJ, Rojas B, Ajoy D, López-Cuenca I, Rojas P, Triviño A, Ramírez JM (2017) The role of microglia in retinal neurodegeneration: Alzheimer's disease, Parkinson, and Glaucoma. Front Aging Neurosci 9:214.  https://doi.org/10.3389/fnagi.2017.00214 CrossRefPubMedPubMedCentralGoogle Scholar
  125. Rapoport M, Dawson HN, Binder LI, Vitek MP, Ferreira A (2002) Tau is essential to beta-amyloid-induced neurotoxicity. Proc Natl Acad Sci USA 99:6364–6369PubMedCrossRefPubMedCentralGoogle Scholar
  126. Ratican SE, Osborne A, Martin KR (2018) Progress in gene therapy to prevent retinal ganglion cell loss in glaucoma and Leber’s hereditary optic neuropathy. Neural Plast.  https://doi.org/10.1155/2018/7108948 CrossRefPubMedPubMedCentralGoogle Scholar
  127. Raval AP, Lin HW, Dave KR, Defazio RA, Della Morte D, Kim EJ, Perez-Pinzon MA (2008) Resveratrol and ischemic preconditioning in the brain. Curr Med Chem 15(15):1545–1551PubMedCrossRefPubMedCentralGoogle Scholar
  128. Rege SD, Geetha T, Griffin GD, Broderick TL, Babu JR (2014) Neuroprotective effects of resveratrol in Alzheimer disease pathology. Front Aging Neurosci 6:218PubMedPubMedCentralCrossRefGoogle Scholar
  129. Rodrigues CMP, Sola S, Silva R, Brites D (2000) Bilirubin and amyloid-beta peptide induce cytochrome c release through mitochondrial membrane permeabilization. Mol Med 6:936–946PubMedPubMedCentralCrossRefGoogle Scholar
  130. Roher AE, Lowenson JD, Clarke S, Woods AS, Cotter RJ, Gowing E, Ball MJ (1993) beta-Amyloid-(1–42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc Natl Acad Sci USA 90(22):10836–10840PubMedCrossRefPubMedCentralGoogle Scholar
  131. Rohn TT, Head E (2009) Caspases as therapeutic targets in Alzheimer's disease: is it time to "cut" to the chase? Int J Clin Exp Pathol 2(2):108–118PubMedPubMedCentralGoogle Scholar
  132. Sadun AA, Bassi CJ (1990) Optic nerve damage in Alzheimer’s disease. Ophthalmology 97:9–17PubMedCrossRefPubMedCentralGoogle Scholar
  133. Sale JM, Anna VA (2014) Resurreccion, resveratrol in peanuts. Crit Rev Food Sci Nutr 54(6):734–770CrossRefGoogle Scholar
  134. Sandhu P, Naeem MM, Lu C, Kumarathasan P, Gomes J, Basak A (2017) Ser422 phosphorylation blocks human Tau cleavage by caspase-3: biochemical implications to Alzheimer's Disease. Bioorg Med Chem Lett 27(3):642–652PubMedCrossRefPubMedCentralGoogle Scholar
  135. Saxena S, Caroni P (2011) Selective neuronal vulnerability in neurodegenerative diseases: From stressor thresholds to degeneration. Neuron 71:35–48PubMedCrossRefPubMedCentralGoogle Scholar
  136. Schneider M, Fuchshofer R (2015a) The role of astrocytes in optic nerve head fibrosis in glaucoma. Exp Eye Res 142:49–55PubMedCrossRefPubMedCentralGoogle Scholar
  137. Schneider M, Fuchshofer R (2015b) The role of astrocytes in optic nerve head fibrosis in glaucoma. Exp Eye Res 142:49–55PubMedCrossRefPubMedCentralGoogle Scholar
  138. Schneider M, Fuchshofer R (2016) The role of astrocytes in optic nerve head fibrosis in glaucoma. Exp Eye Res 142:49–55PubMedCrossRefPubMedCentralGoogle Scholar
  139. Schön C, Hoffmann NA, Ochs SM, Burgold S, Filser S, Steinbach S, Seeliger MW, Arzberger T, Goedert M, Kretzschmar HA, Schmidt B, Herms J (2012) Long-term in vivo imaging of fibrillar tau in the retina of P301S transgenic mice. PLoS ONE 7(12):e53547.  https://doi.org/10.1371/journal.pone.0053547 CrossRefPubMedPubMedCentralGoogle Scholar
  140. Sivak JM (2013a) The aging eye: common degenerative mechanisms between the Alzheimer’s brain and retinal disease. Investig Ophthalmol Vis Sci 54(1):871–880CrossRefGoogle Scholar
  141. Sivak J (2013b) The aging eye: common degenerative mechanisms between the Alzheimer's brain and retinal disease. Investig Ophthalmol Vis Sci 54:871–880CrossRefGoogle Scholar
  142. Smale G, Nichols NR, Brady DR, Finch CE, Horton WE Jr (1995) Evidence for apoptotic cell death in Alzheimer's disease. Exp Neurol 133:225–230PubMedCrossRefPubMedCentralGoogle Scholar
  143. Sofroniew MV, Vinters HV (2009) Astrocytes: biology and pathology. Acta Neuropathol 119(1):7–35PubMedPubMedCentralCrossRefGoogle Scholar
  144. Soto I, Howell GR (2014) The complex role of neuroinflammation in glaucoma. Cold Spring Harb Perspect Med 4(8):17269CrossRefGoogle Scholar
  145. Sriram K, Benkovic SA, Hebert MA, Miller DB, O'Callaghan JP (2004) Induction of gp130-related cytokines and activation of JAK2/STAT3 pathway in astrocytes precedes up-regulation of glial fibrillary acidic protein in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of neurodegeneration: key signaling pathway for astrogliosis in vivo? J Biol Chem 279:19936–19947PubMedCrossRefPubMedCentralGoogle Scholar
  146. Suk K, Lee J, Hur J, Kim YS, Lee M, Cha S, Yeou Kim S, Kim IH (2001) Activation-induced cell death of rat astrocytes. Brain Res 900:342–347PubMedCrossRefPubMedCentralGoogle Scholar
  147. Sun AY, Wang Q, Simonyi A, Sun GY (2010) Resveratrol as a therapeutic agent for neurodegenerative diseases. Mol Neurobiol 41(2–3):375–383PubMedPubMedCentralCrossRefGoogle Scholar
  148. Sun D, Qu J, Jakobs TC (2013) Reversible reactivity by optic nerve astrocytes. Glia 61(8):1218–1235PubMedPubMedCentralCrossRefGoogle Scholar
  149. Sun D, Moore S, Jakobs TC (2017) Optic nerve astrocyte reactivity protects function in experimental glaucoma and other nerve injuries. J Exp Med 214(5):1411–1430PubMedPubMedCentralCrossRefGoogle Scholar
  150. Tezel G (2006) Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences. Prog Retin Eye Res 25:490–513PubMedPubMedCentralCrossRefGoogle Scholar
  151. Tezel G (2009) The role of glia, mitochondria, and the immune system in glaucoma. Investig Ophthalmol Vis Sci 50:1001–1012CrossRefGoogle Scholar
  152. Tezel G (2013) Immune regulation toward immunomodulation for neuroprotection in glaucoma. Curr Opin Pharmacol 13:23–31PubMedCrossRefPubMedCentralGoogle Scholar
  153. Trapp V, Parmakhtiar B, Papazian V, Willmott L, Fruehauf JP (2010) Anti-angiogenic effects of resveratrol mediated by decreased VEGF and increased TSP1 expression in melanoma-endothelial cell co-culture. Angiogenesis 13(4):305–315PubMedPubMedCentralCrossRefGoogle Scholar
  154. Tsolaki F, Gogaki E, Tiganita S, Skatharoudi C, Lopatatzidi C, Topouzis F, Tsolaki M (2011) Alzheimer’s disease and primary open-angle glaucoma: is there a connection? Clin Ophthalmol 5:887–890PubMedPubMedCentralCrossRefGoogle Scholar
  155. Uttara B, Singh AV, Zamboni P, Mahajan RT (2009) Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 7:65–74PubMedPubMedCentralCrossRefGoogle Scholar
  156. Wälti MA, Ravotti F, Arai H, Glabe CG, Wall JS, Böckmann A, Güntert P, Meier BH, Riek R (2016) Atomic-resolution structure of a disease-relevant Aβ (1–42) amyloid fibril. Proc Natl Acad Sci USA 113(34):E4976–4984PubMedCrossRefPubMedCentralGoogle Scholar
  157. Wang L, Cioffi GA, Cull G, Dong J, Fortune B (2002) Immunohistologic evidence for retinal glial cell changes in human glaucoma. Invest Ophthalmol Vis Sci 43(4):1088–1094PubMedPubMedCentralGoogle Scholar
  158. Wang Y, Yin H, Wang L, Shuboy A, Lou J, Han B, Zhang X, Li J (2013) Curcumin as a potential treatment for Alzheimer's disease: a study of the effects of curcumin on hippocampal expression of glial fibrillary acidic protein. Am J Chin Med 41(1):59–70PubMedCrossRefPubMedCentralGoogle Scholar
  159. Weinreb RN, Aung T, Medeiros FA (2014) The pathophysiology and treatment of glaucoma: a review. JAMA 311(18):1901–1911PubMedPubMedCentralCrossRefGoogle Scholar
  160. Wostyn P, Audenaert K, De Deyn PP (2009) Alzheimer’s disease and glaucoma: Is there a causal relationship? Br J Ophthalmol 93:1557–1559PubMedCrossRefGoogle Scholar
  161. Wu A, Chiu K, Chan V, Chang R (2011) A review of the Alzheimer’s disease animal models and retinal degeneration. J Undergrad Res AltaGoogle Scholar
  162. Wu X, Piña-Crespo J, Zhang Y, Huaxi C, Huaxi X (2017) Tau-mediated neurodegeneration and potential implications in diagnosis and treatment of Alzheimer's disease. Chin Med J.  https://doi.org/10.4103/0366-6999.220313 CrossRefPubMedPubMedCentralGoogle Scholar
  163. Xu P, Zhang X, Zhang H (2011) Expression and significance of phosphorylated tau protein in the optic nerve of chronic ocular hypertension rats model. Ophthalmol China 20:367–372Google Scholar
  164. Yang Y, Yu M, Zhu J, Chen X, Liu X (2009) Role of cerebrospinal fluid in glaucoma: pressure and beyond. Med Hypotheses 74:31–34PubMedCrossRefPubMedCentralGoogle Scholar
  165. Yoneda S, Hara H, Hirata A, Fukushima M, Inomata Y, Tanihara H (2005) Vitreous fluid levels of beta-amyloid (1–42) and tau in patients with retinal diseases. Jpn J Ophthalmol 49(2):106–108PubMedCrossRefPubMedCentralGoogle Scholar
  166. Yu AC, Lee YL, Eng LF (1993) Astrogliosis in culture: I The model and the effect of antisense oligonucleotides on glial fibrillary acidic protein synthesis. J Neurosci Res 34(3):295–303PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Vision Research Center, Department of Ophthalmology, School of MedicineUniversity of Missouri –Kansas CityKansas CityUSA
  2. 2.Department of Biomedical Sciences, School of MedicineUniversity of Missouri –Kansas CityKansas CityUSA

Personalised recommendations