Fundus Camera-Delivered Light-Induced Retinal Degeneration in Mice With the RPE65 Leu450Met Variant is Associated With Oxidative Stress and Apoptosis
| Autor: | Kaiyan Zhang, Cynthia X. Zhao, Bogale Aredo, Yi Ding, Rafael Ufret-Vincenty, Xin Zhong |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Retinal degeneration cis-trans-Isomerases Pathology medicine.medical_specialty Light Fundus Oculi Apoptosis RPE65 Real-Time Polymerase Chain Reaction Retina 03 medical and health sciences chemistry.chemical_compound Mice medicine In Situ Nick-End Labeling Animals Fluorescein Angiography medicine.diagnostic_test business.industry Retinal Degeneration Retinal Macular degeneration light damage Fluorescein angiography medicine.disease Immunohistochemistry eye diseases 3. Good health Mice Inbred C57BL Disease Models Animal Oxidative Stress 030104 developmental biology medicine.anatomical_structure Leu450Met chemistry Gene Expression Regulation Cis-trans-Isomerases RNA sense organs Microglia business Retinal Dystrophies Tomography Optical Coherence Photoreceptor Cells Vertebrate |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 0146-0404 |
| Popis: | Purpose Oxidative stress, partly due to light, has an important role in many retinal diseases, including macular degeneration and retinal dystrophies. The Leu450Met variant of RPE65 is expressed in C57BL/6 and in many genetically modified mice. It confers significant resistance to light induced retinal degeneration (LIRD). Our goal was to develop an effective and efficient method to induce LIRD in resistant mice that would recapitulate mechanisms seen in known models of LIRD. Methods The retinas of C57BL/6J mice were exposed to light using a murine fundus camera. Two protocols (with and without intraperitoneal fluorescein) were used. Optical coherence tomography (OCT) helped determine the location and extent of retinal damage. Histology, TUNEL assay, quantitative (q) PCR, and immunohistochemistry were performed. Results Both protocols consistently generated LIRD in C57BL/6J mice. Optical coherence tomography and histology demonstrated that retinal damage starts at the level of the photoreceptor/outer retina and is more prominent in the superior retina. Fundus camera-delivered light-induced retinal degeneration (FCD-LIRD) is associated with apoptosis, subretinal microglia/macrophages, increased expression of oxidative stress response genes, and C3d deposition. Conclusions We characterize two new models of light-induced retinal degeneration that are effective in C57BL/6J mice, and can be modulated in terms of severity. We expect FCD-LIRD to be useful in exploring mechanisms of LIRD in resistant mice, which will be important in increasing our understanding of the retinal response to light damage and oxidative stress. |
| Databáze: | OpenAIRE |
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