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Tadao Maeda, kiichiro Okano, Yu Chen, Tsutomu Sakai, Krzysztof Palczewski, Akiko Maeda; Dysfunction Of Retinal Cells By All-trans-retinal And Its Condensation Product A2E. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3357.
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© ARVO (1962-2015); The Authors (2016-present)
High levels of all–trans–retinal and its associated condensation products can cause retinal degeneration in a light–dependent manner, and contribute to the pathogenesis of human macular diseases such as age–related macular degeneration (AMD) and Stargardt’s disease. In this study, we evaluate retinal cell dysfunction mediated by accumulation of potentially toxic all-trans-retinal and its condensation product, diretinoid-pyridinium-ethanolamine (A2E).
Transgenic mice with rod-only or cone-like only retina were prepared by genetically ablating cone-DTA (cone-specific diphtheria toxin A) transgene or deletion of Nrl (rod photoreceptor-specific neural retina leucine zipper protein gene). We examined these mice in addition to the progenies of such mice crossbred with Rdh8 and Abca4 deficient mice manifesting severe light-induced retinal dystrophy. Age– or light–dependent changes in retinal function and morphology were evaluated by electroretinogram, scanning laser ophthalmoscope (SLO) and spectral domain-optical coherence tomography (SD-OCT). RPE function and morphology were evaluated by two-photon microscopy, immuhohistochemistry and biochemical methods.
Among these strains, Rdh8–/–Abca4–/– mice with a mixed rod–cone population showed the most severe retinal degeneration under regular cyclic light. Intense light exposure induced acute retinal damage in Rdh8–/–Abca4–/– mice and rod–only mice whereas this change was not observed in cone–like–only mice. Different
Rods, cones and RPEs exhibit their characteristic dysfunction by excess levels of all-trans-retinal and A2E, which dictates the unique pathology observed in retinal degenerative Rdh8–/–Abca4–/–mice.
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