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. 2011 Jan;3(1):44-54.
doi: 10.18632/aging.100243.

Alterations of Retinal Pigment Epithelium Cause AMD-like Retinopathy in Senescence-Accelerated OXYS Rats

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Free PMC article

Alterations of Retinal Pigment Epithelium Cause AMD-like Retinopathy in Senescence-Accelerated OXYS Rats

Anton M Markovets et al. Aging (Albany NY). .
Free PMC article

Abstract

Pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the world, remains poorly understood. This makes it necessary to create animal models for studying AMD pathogenesis and to design new therapeutic approaches. Here we showed that retinopathy in OXYS rats is similar to human AMD according to clinical signs, morphology, and vascular endothelium growth factor (VEGF) and pigment epithelium-derived factor (PEDF) genes expression. Clinical signs of retinopathy OXYS rats manifest by the age 3 months against the background of significantly reduced expression level of VEGF and PEDF genes due to the decline of the amount of retinal pigment epithelium (RPE) cells and alteration of choroidal microcirculation. The disruption in OXYS rats' retina starts at the age of 20 days and appears as reduce the area of RPE cells but does not affect their ultrastructure. Ultrastructural pathological alterations of RPE as well as develop forms of retinopathy are observed in OXYS rats from age 12 months and manifested as excessive accumulation of lipofuscin in RPE regions adjacent to the rod cells, whirling extentions of the basement membrane into the cytoplasm. These data suggest that primary cellular degenerative alterations in the RPE cells secondarily lead to choriocapillaris atrophy and results in complete loss of photoreceptor cells in the OXYS rats' retina by the age of 24 months.

Conflict of interest statement

The authors of this manuscript have no conflict of interests to declare.

Figures

Figure 1.
Figure 1.. Distribution of the stages of development of retinopathy in eyes of OXYS rats.
0 − 3 – corresponding stage of the retinopathy according to Age-Related Eye Disease Study grade protocol (eyephoto.ophth.wisc.edu). 790 animals were examined in total.
Figure 2.
Figure 2.
Outer retina of Wistar (a) and OXYS (b) rats at the age of 3 months. PRL – photoreceptors, RPE – retinal pigment epithelial cell, N – RPE nucleus, m – mitochondrion, Ph – phagosome, Lip – lipofuscin material, BM – Bruch's membrane, Endo – endothelial cell, RBC – red blood cell.
Figure 3.
Figure 3.
Outer retina of Wistar (a) and OXYS (b) rats at the age of 12 months. Arrows show thickening of Brunch membrane. RPE – retinal pigment epithelial cell, N – RPE nucleus, m – mitochondrion, BM – Bruch's membrane, ChC – choriocapillaris complex, RBC – red blood cell.
Figure 4.
Figure 4.
(a) Ultrastructure of pigment epithelium of 25-months-old OXYS rat. Selected area is shown under high magnification. Lip – lipofuscin material, N – retinal pigment epithelial cell nucleus. (b) Region of pigment epithelium of 25-months-old OXYS rat. Retina injure was estimated as 3 units. INL – inner nuclear layer, where the body and nucleus of interneurones is lied; OPL – outer plexiform layer – where axon of photoreceptor and dendrite of interneurone are in contact; ONL – outer nuclear layer, body and nucleus of photoreceptors; PRL – photoreceptors, RPE – retinal pigment epithelial cell. Arrow shown the blood vessel.
Figure 5.
Figure 5.. Ultrastructure of outer retina of Wistar rat at the age of 25 months.
PRL – photoreceptors, RPE – retinal pigment epithelial cell, N – RPE nucleus, Lip – lipo-fuscin material, BM – Bruch's membrane, Endo – endothelial cell, RBC – red blood cell.
Figure 6.
Figure 6.
Age-related changes of the average area of RPE cells (a) and specific area of vessels with stasis and thrombosis (b) in the retinas' sections of OXYS and Wistar rats. *interstrain differences; ^differences in comparison with previous age; p<0.05. Data presented as mean ± S.E.M.
Figure 7.
Figure 7.
Messenger RNA (mRNA) expression of (a) vascular endothelium growth factor (VEGF) and (b) pigment epithelium-derived factor (PEDF) in retina determined by real-time polymerase chain reaction (PCR), N=5. Data presented as mean ± S.E.M. *interstrain differences; ^differences in comparison with previous age; p<0.05.

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References

    1. Strauss O. The retinal pigment epithelium in visual function. Physiol Rev. 2005;85:845–881. - PubMed
    1. Strunnikova NV, Maminishkis A, Barb JJ, Wang F, Zhi C, Sergeev Y, Chen W, Edwards AO, Stambolian D, Abecasis G, Swaroop A, Munson PJ, Miller SS. Transcriptome analysis and molecular signature of human retinal pigment epithelium. Hum Mol Genet. 2010;19:2468–2486. - PMC - PubMed
    1. Korte GE, Gerszberg T, Pua F, Henkind P. Choriocapillaris atrophy after experimental destruction of the retinal pigment epithelium in the rat. A study in thin sections and vascular casts. Acta Anat (Basel) 1986;127:171–175. - PubMed
    1. McLeod DS, Grebe R, Bhutto I, Merges C, Baba T, Lutty GA. Re lationship between RPE and choriocapillaris in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2009;50:4982–4991. - PMC - PubMed
    1. Tombran-Tink J, Shivaram SM, Chader GJ, Johnson LV, Bok D. Expression, secretion, and age-related downregulation of pigment epithelium-derived factor, a serpin with neurotrophic activity. J Neurosci. 1995;15:4992–5003. - PMC - PubMed

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