Two-photon microscopy reveals early rod photoreceptor cell damage in light-exposed mutant mice.
Atrophic age-related and juvenile macular degeneration are especially devastating due to lack of an effective cure. Two retinal cell types, photoreceptor cells and the adjacent retinal pigmented epithelium (RPE), reportedly display the earliest pathological changes. Abca4(-/-)Rdh8(-/-) mice, which mimic many features of human retinal degeneration, allowed us to determine the sequence of light-induced events leading to retinal degeneration. Using two-photon microscopy with 3D reconstruction methodology, we observed an initial strong retinoid-derived fluorescence and expansion of Abca4(-/-)Rdh8(-/-) mouse rod cell outer segments accompanied by macrophage infiltration after brief exposure of the retina to bright light. Additionally, light-dependent fluorescent compounds produced in rod outer segments were not transferred to the RPE of mice genetically defective in RPE phagocytosis. Collectively, these findings suggest that for light-induced retinopathies in mice, rod photoreceptors are the primary site of toxic retinoid accumulation and degeneration, followed by secondary changes in the RPE.
Departments of Pharmacology and Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106.
Akiko
A
Maeda
Grazyna
G
Palczewska
Marcin
M
Golczak
Hideo
H
Kohno
Zhiqian
Z
Dong
Tadao
T
Maeda
Krzysztof
K
Palczewski
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000429:Alcohol Oxidoreductases / Q000235:genetics; D000818:Animals; D008027:Light; D051379:Mice; D008817:Mice, Mutant Strains; D017628:Microglia / Q000378:metabolism; D008853:Microscopy / Q000379:methods*; D010587:Phagocytosis; D017785:Photons; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000528:radiation effects; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000528:radiation effects*; D012176:Retinoids / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D000429:Alcohol Oxidoreductases; D017382:Reactive Oxygen Species; D012176:Retinoids; C512841:Abca4 protein, mouse; C525880:HSD17B6 protein, mouse