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 mim...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2014-04, Vol.111 (14), p.E1428-E1437
Main Authors: Maeda, Akiko, Palczewska, Grazyna, Golczak, Marcin, Kohno, Hideo, Dong, Zhiqian, Maeda, Tadao, Palczewski, Krzysztof
Format: Article
Language:English
Subjects:
Alcohol Oxidoreductases - genetics
Animals
ATP-Binding Cassette Transporters - genetics
Biological Sciences
Cells
DNA damage
Light
Macular degeneration
Mice
Mice, Mutant Strains
Microglia - metabolism
Microscopy - methods
Mutation
Phagocytosis
Photons
PNAS Plus
Reactive Oxygen Species - metabolism
Retina - metabolism
Retina - radiation effects
Retinal Rod Photoreceptor Cells - cytology
Retinal Rod Photoreceptor Cells - radiation effects
Retinoids - metabolism
Rodents
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1317986111