Abstract
The eye is a special sensory organ, which is basically an extension of the brain. Both are derived from neural tube and consist of neurons. Therefore, diseases of both the brain and eye should have some similarity. Neurodegenerative disorders like Alzheimer’s disease (AD) is the major cause of dementia in the world. Amyloid deposition in the cerebral cortex and hippocampal region is the basic pathology in AD. But along with it, there are various changes that take place in the eye, i.e., abnormal pupillary reaction, decreased vision, decreased contrast sensitivity, visual field changes, loss of retinal ganglionic cells and retinal fiber layer, peripapillary atrophy, increased cup-disk ratio, retinal thinning, tortuosity of blood vessels, and deposition of Aβ-like substance in the retina. And these changes are present in the early part of the disease when only mild cognitive impairment is there. As the brain is covered by a hard bony skull which makes it difficult to directly visualize the changes occurring in the brain at molecular levels, finer details of disease progression are not available with us. But the eye is the window of the brain; with advanced modern techniques, we can directly visualize the changes in the retina at a very fine level. Therefore, by depicting neurodegenerative changes in the eye, we can diagnose and manage AD at very early stages. Along with it, retinal neurodegenerations like glaucoma and age-related macular degeneration (ARMD) are the major cause of loss of vision, and still, there are no effective treatment modalities for these blinding conditions. So if we can understand its pathogenesis and progression by correlating with brain neurodegenerations, we can come up with a better therapy for glaucoma and ARMD.
Similar content being viewed by others
References
Barber AG (2003) A new view of diabetic retinopathy: a neurodegenerative disease of the eye. Prog Neuropsychopharmacol Biol Psychiatry 27:283–290
Asnaghi V, Gerhardinger C, Hoehn T, Adeboje A, Lorenzi M (2003) A role of the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes 52:506–511
Abu-El-Asar AM, Dralands L, Missoten L, Al-Jadaan IA, Geboes K (2004) Expression of apoptosis markers in the retinas of human subjects with diabetes. Invest Ophthalmol Vis Sci 45:2760–2766
Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer’s disease. Lancet 368:387–403
Alzheimer’s Association (2005) Newest estimate of worldwide prevalence of Alzheimer’s disease = 26.6 million 2006. In: The 2nd Alzheimer’s Association international conference on prevention of dementia, Washington DC
Davatzikos C, Resnick SM, Wu X, Parmpi P, Clark CM (2008) Individual patient diagnosis of AD and FTD via high-dimensional pattern classification of MRI. NeuroImage 41(4):1199–1205
Jagust WJ, Seab JP, Huesman RH, Valk PE, Mathis CA, Reed BR et al (1991) Diminished glucose transport in Alzheimer’s disease: dynamic PET studies. J Cereb Blood Flow Metab 11:323–330
Bouwman FH, Schoonenboom NS, Verwey NA, van Elk EJ, Kok A, Blankenstein MA et al (2009) CSF biomarker levels in early and late onset Alzheimer’s disease. Neurobiol Aging 30(12):1895–1901
Diniz BS, Pinto JA Jr, Forlenza OV (2007) Do CSF total tau, phosphorylated tau, and beta-amyloid 42 help to predict progression of mild cognitive impairment to Alzheimer’s disease? A systematic review and meta-analysis of the literature. World J Biol Psychiatry 1–119(3):172–182
Scinto LF, Daffner KR, Dressler D, Ransil BI, Rentz D, Weintraub S et al (1994) A potential noninvasive neurobiological test for Alzheimer’s disease. Science (New York, NY) 266:1051–1054
Gomez-Tortosa E, del Barrio A, Jimenez-Alfaro I (1996) Pupil response to tropicamide in Alzheimer’s disease and other neurodegenerative disorders. Acta Neurol Scand 94:104–109
Higuchi S, Matsushita S, Hasegawa Y, Muramatsu T, Arai H (1997) Pupillary response to tropicamide in Japanese patients with alcoholic dementia, Alzheimer’s disease, and vascular dementia. Exp Neurol 144:199–201
Iijima A, Haida M, Ishikawa N, Ueno A, Minamitani H, Shinohara Y (2003) Re-evaluation of tropicamide in the pupillary response test for Alzheimer’s disease. Neurobiol Aging 24:789–796
Scinto LF (2008) Pupillary cholinergic hypersensitivity predicts cognitive decline in community dwelling elders. Neurobiol Aging 29:222–230
Fotiou DF, Brozou CG, Haidich AB, Tsiptsios D, Nakou M, Kabitsi A et al (2007) Pupil reaction to light in Alzheimer’s disease: evaluation of pupil size changes and mobility. Aging Clin Exp Res 19:364–371
Fotiou F, Fountoulakis KN, Tsolaki M, Goulas A, Palikaras A (2000) Changes in pupil reaction to light in Alzheimer’s disease patients: a preliminary report. Int J Psychophysiol 37:111–120
Goldstein LE, Muffat JA, Cherny RA, Moir RD, Ericsson MH, Huang X et al (2003) Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer’s disease. Lancet 361:1258–1265
McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K et al (1999) Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer’s disease. Ann Neurol 46:860–866
Moncaster JA, Moir RD, Mocofanescu A, Burton M, Fu L, Xu W, et al. (2008) In vivo early detection of Alzheimer’s disease-linked ab peptide accumulation in the lens using quasi elastic light scattering ARVO
Frederikse PH, Garland D, Zigler JS Jr, Piatigorsky J (1994) Oxidative stress increases production of beta-amyloid precursor protein and beta-amyloid (Abeta) in mammalian lenses, and Abeta has toxic effects on lens epithelial cells. J Biol Chem 271:10169–10174
Li G, Percontino L, Sun Q, Qazi AS, Frederikse PH (2003) Beta-amyloid secretases and beta-amyloid degrading enzyme expression in lens. Mol Vis 9:179–183
Sadun AA, Borchert M, DeVita E, Hinton DR, Bassi CJ (1987) Assessment of visual impairment in patients with Alzheimer’s disease. Am J Ophthalmol 104:113–120
Katz B, Rimmer S (1989) Ophthalmologic manifestations of Alzheimer’s disease. Surv Ophthalmol 34:31–43
Cronin-Golomb A, Corkin S, Rizzo JF, Cohen J, Growdon JH, Banks KS (1991) Visual dysfunction in Alzheimer’s disease: relation to normal aging. Ann Neurol 29:41–52
Mendez MF, Cherrier MM, Meadows RS (1996) Depth perception in Alzheimer’s disease. Percept Mot Skills 83:987–995
Hinton DR, Sadun AA, Blanks JC, Miller CA (1986) Optic-nerve degeneration in Alzheimer’s disease. N Engl J Med 315:485–487
Livingstone MS, Hubel DH (1987) Psychophysical evidence for separate channels for the perception of form, color, movement, and depth. J Neurosci 7:3416–3468
Jackson GR, Owsley C (2003) Visual dysfunction, neurodegenerative diseases, and aging. Neurol Clin 21:709–728
Sadun AA, Bassi CJ (1990) Optic nerve damage in Alzheimer’s disease. Ophthalmology 97:9–17
Blanks JC, Hinton DR, Sadun AA, Miller CA (1989) Retinal ganglion cell degeneration in Alzheimer’s disease. Brain Res 501:364–372
Blanks JC, Schmidt SY, Torigoe Y, Porrello KV, Hinton DR, Blanks RH (1996) Retinal pathology in Alzheimer’s disease. II. Regional neuron loss and glial changes in GCL. Neurobiol Aging 17:385–395
Blanks JC, Torigoe Y, Hinton DR, Blanks RH (1996) Retinal pathology in Alzheimer’s disease. I. Ganglion cell loss in foveal/parafoveal retina. Neurobiol Aging 17:377–384
Loffler KU, Edward DP, Tso MO (1995) Immunoreactivity against tau, amyloid precursor protein, and beta-amyloid in the human retina. Invest Ophthalmol Vis Sci 36:24–31
Perez SE, Lumayag S, Kovacs B, Mufson EJ, Xu S (2009) {beta}-amyloid deposition and functional impairment in the retina of the APPswe/PS1{Delta}E9 transgenic mouse model of Alzheimer’s disease. Invest Ophthalmol Vis Sci 50(2):793–800
Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W et al (1991) Optical coherence tomography. Science (New York, NY) 254:1178–1181
Iseri PK, Altinas O, Tokay T, Yuksel N (2006) Relationship between cognitive impairment and retinal morphological and visual functional abnormalities in Alzheimer disease. J Neuroophthalmol 26:18–24
Parisi V (2003) Correlation between morphological and functional retinal impairment in patients affected by ocular hypertension, glaucoma, demyelinating optic neuritis and Alzheimer’s disease. Semin Ophthalmol 18:50–57
Parisi V, Restuccia R, Fattapposta F, Mina C, Bucci MG, Pierelli F (2001) Morphological and functional retinal impairment in Alzheimer’s disease patients. Clin Neurophysiol 112:1860–1867
Berisha F, Feke GT, Trempe CL, McMeel JW, Schepens CL (2007) Retinal abnormalities in early Alzheimer’s disease. Invest Ophthalmol Vis Sci 48:2285–2289
Katz B, Rimmer S, Iragui V, Katzman R (1989) Abnormal pattern electroretinogram in Alzheimer’s disease: evidence for retinal ganglion cell degeneration? Ann Neurol 26:221–225
Hollander H, Bisti S, Maffei L, Hebel R (1996) Electroretinographic responses and retrograde changes of retinal morphology after intracranial optic nerve section. A quantitative analysis in the cat. Exp Brain Res Exp Hirnforsch 55:483–493
Danesh-Meyer HV, Birch H, Ku JY, Carroll S, Gamble G (2006) Reduction of optic nerve fibers in patients with Alzheimer disease identified by laser imaging. Neurology 67:1852–1854
Tsai CS, Ritch R, Schwartz B, Lee SS, Miller NR, Chi T et al (1991) Optic nerve head and nerve fiber layer in Alzheimer’s disease. Arch Ophthalmol 109:199–204
Ruitenberg A, den Heijer T, Bakker SL, van Swieten JC, Koudstaal PJ, Hofman A et al (2005) Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol 57:789–794
Cordeiro MF, Guo L, Luong V, Harding G, Wang W, Jones HE et al (2004) Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration. Proc Natl Acad Sci U S A 101:13352–13356
Guo L, Salt TE, Luong V, Wood N, Cheung W, Maass A et al (2007) Targeting amyloid-beta in glaucoma treatment. Proc Natl Acad Sci U S A 104:13444–13449
Oliver JE, Hattenhauer MG, Herman D, Hodge DO, Kennedy R, Fang-Yen M et al (2002) Blindness and glaucoma: a comparison of patients progressing to blindness from glaucoma with patients maintaining vision. Am J Ophthalmol 133:764–772
Collaborative Normal-Tension Glaucoma Study Group T (1998) Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol 126:487–497
Bayer AU, Ferrari F, Erb C (2002) High occurrence rate of glaucoma among patients with Alzheimer’s disease. Eur Neurol 47:165–168
Bayer AU, Keller ON, Ferrari F, Maag KP (2002) Association of glaucoma with neurodegenerative diseases with apoptotic cell death: Alzheimer’s disease and Parkinson’s disease. Am J Ophthalmol 133:135–137
Tamura H, Kawakami H, Kanamoto T, Kato T, Yokoyama T, Sasaki K et al (2006) High frequency of open-angle glaucoma in Japanese patients with Alzheimer’s disease. J Neurol Sci 246:79–83
Bayer AU, Ferrari F (2002) Severe progression of glaucomatous optic neuropathy in patients with Alzheimer’s disease. Eye 16:209–212
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 49:106–108
Blennow K, Hampel H (2003) CSF markers for incipient Alzheimer’s disease. Lancet Neurol 2:605–613
Strozyk D, Blennow K, White LR, Launer LJ (2003) CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology 60:652–656
Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D et al (1995) Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer’s disease. Ann Neurol 38:643–648
McKinnon SJ, Lehman DM, Kerrigan-Baumrind LA, Merges CA, Pease ME, Kerrigan DF et al (2002) Caspase activation and amyloid precursor protein cleavage in rat ocular hypertension. Invest Ophthalmol Vis Sci 43:1077–1087
Gupta N, Fong J, Ang LC, Yucel YH (2008) Retinal tau pathology in human glaucomas. Can J Ophthalmol 43:53–60
Crawford ML, Harwerth RS, Smith EL 3rd, Mills S, Ewing B (2001) Experimental glaucoma in primates: changes in cytochrome oxidase blobs in V1 cortex. Invest Ophthalmol Vis Sci 42:358–364
Crawford ML, Harwerth RS, Smith EL 3rd, Shen F, Carter-Dawson L (2000) Glaucoma in primates: cytochrome oxidase reactivity in parvo- and magnocellular pathways. Invest Ophthalmol Vis Sci 41:1791–1802
Yucel YH, Zhang Q, Gupta N, Kaufman PL, Weinreb RN (2000) Loss of neurons in magnocellular and parvocellular layers of the lateral geniculate nucleus in glaucoma. Arch Ophthalmol 118:378–384
Yucel YH, Zhang Q, Weinreb RN, Kaufman PL, Gupta N (2001) Atrophy of relay neurons in magno- and parvocellular layers in the lateral geniculate nucleus in experimental glaucoma. Invest Ophthalmol Vis Sci 42:3216–3222
Yucel YH, Zhang Q, Weinreb RN, Kaufman PL, Gupta N (2003) Effects of retinal ganglion cell loss on magno-, parvo-, koniocellular pathways in the lateral geniculate nucleus and visual cortex in glaucoma. Prog Retin Eye Res 22:465–481
Duncan RO, Sample PA, Weinreb RN, Bowd C, Zangwill LM (2007) Retinotopic organization of primary visual cortex in glaucoma: a method for comparing cortical function with damage to the optic disk. Invest Ophthalmol Vis Sci 48:733–744
Friedman DS, O’Colmain BJ, Munoz B et al (2004) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122:564–572
Klein R, Peto T, Bird A, Vannewkirk MR (2004) The epidemiology of age-related macular degeneration. Am J Ophthalmol 137:486–495
Sparrow JR (2010) Bisretinoids of RPE lipofuscin: trigger for complement activation in age-related macular degeneration. Adv Exp Med Biol 703:63–74
Atwood CS, Martins RN, Smith MA, Perry G (2002) Senile plaque composition and posttranslational modification of amyloidbeta peptide and associated proteins. Peptides 23:1343–1350
Hoh Kam J, Lenassi E, Jeffery G (2010) Viewing ageing eyes: diverse sites of amyloid Beta accumulation in the ageing mouse retina and the up-regulation of macrophages. PLoS One 5, doi:10.1371/journal.pone.0013127
Dentchev T, Milam AH, Lee VM, Trojanowski JQ, Dunaief JL (2003) Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas. Mol Vis 9:184–190
Johnson LV, Leitner WP, Rivest AJ, Staples MK, Radeke MJ, Anderson DH (2002) The Alzheimer’s A beta-peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci U S A 99:11830–11835
Yoshida T, Ohno-Matsui K, Ichinose S et al (2005) The potential role of amyloid beta in the pathogenesis of age-related macular degeneration. J Clin Invest 115:2793–2800
Seddon JM, Ajani UA, Mitchell BD (1997) Familial aggregation of age-related maculopathy. Am J Ophthalmol 123:199–206
Souied EH, Benlian P, Amouyel P, Feingold J, Lagarde JP, Munnich A et al (1998) The epsilon4 allele of the apolipoprotein E gene as a potential protective factor for exudative age-related macular degeneration. Am J Ophthalmol 125:353–359
Russ MO, Cleff U, Lanfermann H, Schalnus R, Enzensberger W, Kleinschmidt A (2002) Functional magnetic resonance imaging in acute unilateral optic neuritis. J Neuroimaging 12:339–350
Klaver CC, Kliffen M, van Duijn CM, Hofman A, Cruts M, Grobbee DE et al (1998) Genetic association of apolipoprotein E with age-related macular degeneration. Am J Hum Genet 63:200–206
Baird PN, Guida E, Chu DT, Vu HT, Guymer RH (2004) The epsilon2 and epsilon4 alleles of the apolipoprotein gene are associated with age-related macular degeneration. Invest Ophthalmol Vis Sci 45:1311–1315
Cedazo-Minguez A, Apolipoprotein E (2007) Alzheimer’s disease: molecular mechanisms and therapeutic opportunities. J Cell Mol Med 11:1227–1238
Wong TY, Shankar A, Klein R et al (2006) Apolipoprotein E gene and early age-related maculopathy: the Atherosclerosis Riskin Communities Study. Ophthalmology 113:255–259
Anderson DH, Radeke MJ, Gallo NB et al (2010) The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Prog Retin Eye Res 29:95–112
Edwards AO, Ritter R III, Abel KJ, Manning A, Panhuysen C, Farrer LA (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308:421–424
Johnson LV, Leitner WP, Staples MK, Anderson DH (2001) Complement activation and inflammatory processes in drusen formation and age related macular degeneration. Exp Eye Res 73:887–896
Mullins RF, Russell SR, Anderson DH, Hageman GS (2000) Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J 14:835–846
Umeda S, Suzuki MT, Okamoto H et al (2005) Molecular composition of drusen and possible involvement of anti-retinal autoimmunity in two different forms of macular degeneration in cynomolgus monkey (Macaca fascicularis). FASEB J 19:1683–1685
Eikelenboom P, Stam FC (1982) Immunoglobulins and complement factors in senile plaques. An immunoperoxidase study. Acta Neuropathol 57:239–242
Shen Y, Sullivan T, Lee CM, Meri S, Shiosaki K, Lin CW (1998) Induced expression of neuronal membrane attack complex and cell death by Alzheimer’s beta-amyloid peptide. Brain Res 796:187–197
Strohmeyer R, Shen Y, Rogers J (2000) Detection of complement alternative pathway mRNA and proteins in the Alzheimer’s disease brain. Brain Res Mol Brain Res 81:7–18
Yasojima K, Schwab C, McGeer EG, McGeer PL (1999) Up-regulated production and activation of the complement system in Alzheimer’s disease brain. Am J Pathol 154:927–936
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jindal, V. Interconnection Between Brain and Retinal Neurodegenerations. Mol Neurobiol 51, 885–892 (2015). https://doi.org/10.1007/s12035-014-8733-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-014-8733-6