| First Author | Hu Y | Year | 2011 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 52 |
| Issue | 8 | Pages | 5507-14 |
| PubMed ID | 21551411 | Mgi Jnum | J:181416 |
| Mgi Id | MGI:5311289 | Doi | 10.1167/iovs.10-7118 |
| Citation | Hu Y, et al. (2011) Comparison of ocular pathologies in vitamin A-deficient mice and RPE65 gene knockout mice. Invest Ophthalmol Vis Sci 52(8):5507-14 |
| abstractText | PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: VAD and Rpe65/ mice are different in cone photoreceptor degeneration, photoreceptor-specific gene regulation, isomerohydrolase activity, endogenous retinoid profile, and LRAT activity. |
