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So Goto, Akishi Onishi, Kazuyo Misaki, Shigenobu Yonemura, Hirokazu Sakaguchi, Kohji Nishida, Masayo Takahashi; Retinal degeneration with choroidal hypoplasia in aged Aldh1a1-/- mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3379.
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The pathology of age-related macular degeneration (AMD) is characterized by degeneration in photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris. However, the etiology of AMD remains largely unknown. Since we found that Aldh1a1 knockout (Aldh1a1-/-) mice show choroidal hypoplasia at the dorsal area from embryonic stage (ARVO 2016: Program Number: 965), we characterized changes of photoreceptors and RPE in aged Aldh1a1-/- retinas.
18-month-old Aldh1a1-/- mice and age-matched wild type (WT) mice were used. For morphological characterization, flat mount immunohistochemical analysis of RPE was performed with RPE65, TGFb2, and ZO-1 antibodies. We also performed electron microscope analysis in vertical sections of the posterior eyes. For electrophysiological analysis, single-flash electroretinogram (ERG) was recorded under scoropic and photopic conditions.
Increases in RPE cell size have been observed at the dorsal area of Aldh1a1-/- eyes. The TGFb signals at cytoplasmic region were decreased, and mislocalized at the nucleus in both dorsal and ventral area of Aldh1a1-/- eyes. Electron micrographs of Aldh1a1-/- eyes showed characteristic degeneration signs such as vacuoles and disorganized basal infoldings in the RPE cells, and the fragmentations of photoreceptors. No significant difference was observed in amplitudes and implicit times of ERG responses between WT and Aldh1a1-/- mice.
These results suggest that retinoic acids derived from Aldh1a1 are required for the maintenance of photoreceptors and RPE. The degeneration in retinal photoreceptors and RPE in the aged Aldh1a1-/- mice are reminiscent of geographic atrophy, a characteristic lesion of dry AMD.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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