Purchase this article with an account.
Yang Hu, Ying Chen, Gennadiy Moiseyev, Yusuke Takahashi, Robert Mott, Jian-xing Ma; Comparison of Ocular Pathologies in Vitamin A–Deficient Mice and RPE65 Gene Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(8):5507-5514. doi: 10.1167/iovs.10-7118.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
RPE65 gene knockout (Rpe65 −/−) mice showed abolished isomerohydrolase activity in the visual cycle and were considered a model for vitamin A deficiency in the retina. The purpose of this study was to compare the retinal phenotypes between vitamin A–deficient (VAD) mice and Rpe65 −/− mice under normal diet.
The VAD mice were fed with a vitamin A–deprived diet after birth. The age-matched control mice and Rpe65 −/− mice were maintained under normal diet. The structure of photoreceptor outer segment was compared using electron microscopy. Photoreceptor-specific gene expression was determined using real-time RT-PCR. The isomerohydrolase and lecithin-retinol acyltransferase (LRAT) activities were measured using an in vitro enzymatic activity assay. Endogenous retinoid profiles were analyzed by HPLC in mouse eyecup homogenates.
Compared to wild-type mice under normal diet, scanning and transmission electron microscopy showed that the outer segments of photoreceptors were disorganized in VAD mice and were not disorganized in Rpe65 −/− mice, although they were shortened in the latter. VAD mice showed more prominent downregulation of middle wavelength cone opsin, whereas Rpe65 −/− mice displayed more suppressed expression of short wavelength cone opsin. In vitro enzymatic activity assay and Western blot analysis showed that vitamin A deprivation downregulated LRAT expression and activity in the eyecup, but Rpe65 −/− mice showed unchanged LRAT expression and activity. The depressed LRAT activity in VAD mice was partially rescued by the intraperitoneal injection of retinoic acid.
VAD and Rpe65 −/− mice are different in cone photoreceptor degeneration, photoreceptor-specific gene regulation, isomerohydrolase activity, endogenous retinoid profile, and LRAT activity.
This PDF is available to Subscribers Only