Retinal cone and rod photoreceptor cells exhibit differential susceptibility to light-induced damage.

Abstract

All-trans-retinal and its condensation-products can cause retinal degeneration in a light-dependent manner and contribute to the pathogenesis of human macular diseases such as Stargardt's disease and age-related macular degeneration. Although these toxic retinoid by-products originate from rod and cone photoreceptor cells, the contribution of each cell type to light-induced retinal degeneration is unknown. In this study, the primary objective was to learn whether rods or cones are more susceptible to light-induced, all-trans-retinal-mediated damage. Previously, we reported that mice lacking enzymes that clear all-trans-retinal from the retina, ATP-binding cassette transporter 4 and retinol dehydrogenase 8, manifested light-induced retinal dystrophy. We first examined early-stage age-related macular degeneration patients and found retinal degenerative changes in rod-rich rather than cone-rich regions of the macula. We then evaluated transgenic mice with rod-only and cone-like-only retinas in addition to progenies of such mice inbred with Rdh8(-/-) Abca4(-/-) mice. Of all these strains, Rdh8(-/-) Abca4(-/-) mice with a mixed rod-cone population showed the most severe retinal degeneration under regular cyclic light conditions. Intense light exposure induced acute retinal damage in Rdh8(-/-) Abca4(-/-) and rod-only mice but not cone-like-only mice. These findings suggest that progression of retinal degeneration in Rdh8(-/-) Abca4(-/-) mice is affected by differential vulnerability of rods and cones to light.

• Authors: Kiichiro Okano, Akiko Maeda, Yu Chen, Vishal Chauhan, Johnny Tang, Grazyna Palczewska, Tsutomu Sakai, Hiroshi Tsuneoka, Krzysztof Palczewski, Tadao Maeda
• Journal: Journal of neurochemistry (J Neurochem) Vol. 121 Issue 1 Pg. 146-56 (Apr 2012) ISSN: 1471-4159 [Electronic] England
• PMID: 22220722 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Chemical References

• ATP-Binding Cassette Transporters
• Abca4 protein, mouse
• Alcohol Oxidoreductases
• Rdh8 protein, mouse

Topics

• ATP-Binding Cassette Transporters (drug effects, genetics)
• Aged
• Aged, 80 and over
• Alcohol Oxidoreductases (deficiency, genetics)
• Animals
• Cell Differentiation (physiology)
• Disease Progression
• Female
• Humans
• Macular Degeneration (metabolism, pathology)
• Male
• Mice
• Mice, Transgenic
• Middle Aged
• Photic Stimulation (adverse effects)
• Retinal Cone Photoreceptor Cells (metabolism, pathology)
• Retinal Degeneration (metabolism, pathology)
• Retinal Rod Photoreceptor Cells (metabolism, pathology)