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T Yasukawa, S Hoffmann, U Friedrichs, W Eichler, Y-S Wang, P Wiedemann; A New Model of Age-related Macular Degeneration Induced by Advanced Glycation End Products . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2805.
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Purpose: Recently, it has been reported that advanced glycation end products (AGEs) might be associated with age-related macular degeneration (AMD). The object of this study was to investigate whether a new model of AMD could be developed by subretinal implantation of glycated albumin-microspheres in rabbits. Methods: Glycated albumin was prepared with incubation of rabbit serum albumin (RSA) with glycolaldehyde for 4 hours at 37 degree and used as AGE. AGE-microspheres [MS(AGE)] were made through crosslinking albumin by glycolaldehyde and glutaraldehyde, and non-glycated RSA-microspheres [MS(RSA)] only by glutaraldehyde. Five hundred µg of RSA, AGE, MS(RSA), or MS(AGE) were injected into the subretinal space of rabbit eyes. Eyes were followed up 1, 2, 4, 8 and 12 weeks after operation by ophthalmoscopy and fluorescein angiography. The eyes enucleated 4 or 12 weeks after operation were evaluated by light and fluorescein microscopy. Results: While RSA had no particular effect on the retina, the eyes administered with AGE showed slight fluorescein leakage at week 4, resulting in retinal atrophy at week 12. MS(RSA) exhibited fluorescein leakage on fluorescein angiography at week 8, but histologically only disturbance of retinal cell layer without subretinal neovascularization at week 12. The eyes injected with MS(AGE) showed fluorescein leakage 2 weeks after implantation. This leakage was sustained throughout the following period for observation. In the eyes with MS(AGE) at week 4, histologic examination revealed that there were many microspheres remaining mainly in the cytoplasm of retinal pigment epithelial cells (RPECs), drusen-like and basal laminar deposit-like formations, macrophages adhering to the basal side of retinal pigment epithelium (RPE), and a microspheres-phagocytosing RPEC overlaid with other RPECs. Another eye with MS(AGE) at week 12 showed focal choroidal neovascularization and subsequent severe retinal atrophy. Conclusion: Subretinal implantation of AGE-modified microspheres induced various findings similar to characteristics of AMD. This model may be useful for elucidating the relationship of AGEs with AMD and the pathology of AMD.
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