Retinal cone and rod photoreceptor cells exhibit differential susceptibility to light-induced damage.
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.
Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USA.
Kiichiro
K
Okano
Akiko
A
Maeda
Yu
Y
Chen
Vishal
V
Chauhan
Johnny
J
Tang
Grazyna
G
Palczewska
Tsutomu
T
Sakai
Hiroshi
H
Tsuneoka
Krzysztof
K
Palczewski
Tadao
T
Maeda
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000429:Alcohol Oxidoreductases / Q000172:deficiency / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D010775:Photic Stimulation / Q000009:adverse effects*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*
D018528:ATP-Binding Cassette Transporters; D000429:Alcohol Oxidoreductases; C512841:Abca4 protein, mouse; C525880:HSD17B6 protein, mouse