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Development of Choroidal Neovascularization in Rats With Advanced Intense Cyclic Light–Induced Retinal Degeneration
Daniel M. Albert, MD, MS;
Aneesh Neekhra, MD;
Shoujian Wang, MD, PhD;
Soesiawati R. Darjatmoko, BS;
Christine M. Sorenson, PhD;
Richard R. Dubielzig, DVM;
Nader Sheibani, PhD
Arch Ophthalmol. 2010;128(2):212-222. doi:10.1001/archophthalmol.2009.395
Objectives To study the progressive changes of intense cyclic light–induced retinal degeneration and to determine whether it results in choroidal neovascularization (CNV).
Methods Albino rats were exposed to 12 hours of 3000-lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography, fluorescein and indocyanine green angiography, and optical coherence tomography were performed prior to euthanization. Light-exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal– and nitrotyrosine-modified proteins by immunofluorescence staining.
Results Long-term intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer as well as development of subretinal pigment epithelium neovascularization after 1 month. Almost the entire outer nuclear layer was absent with the presence of CNV, which penetrated the Bruch membrane and extended into the outer retina after 3 months. Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light–exposed animals showed an increased presence of 4-hydroxy-2-nonenal and nitrotyrosine staining. Optical coherence tomographic and angiographic studies confirmed retinal thinning and leakiness of the newly formed blood vessels.
Conclusions Our results suggest that albino rats develop progressive stages of retinal degeneration and CNV after long-term intense cyclic light exposure, allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration.
Clinical Relevance The ability to study the progressive pathogenesis of age-related macular degeneration and CNV will provide detailed knowledge about the disease and aid in the development of target-specific therapy.
Author Affiliations: Departments of Ophthalmology and Visual Sciences (Drs Albert, Neekhra, Wang, and Sheibani and Ms Darjatmoko), Pediatrics (Dr Sorenson), Veterinary Medicine (Dr Dubielzig), and Pharmacology (Dr Sheibani), University of Wisconsin School of Medicine and Public Health, Madison.
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