A novel murine model of age-related macular degeneration induced by combined chronic exposure to light and hydroquinone
Received:March 07, 2019  
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DOI:10. 3969 / j.issn.1005-4847. 2019. 06. 002
KeyWord:age related macular degeneration; mouse model; light exposure; hydroquinone
                 
AuthorInstitution
张晶 中国中医科学院眼科医院,北京
许凯 中国中医科学院眼科医院,北京
梁洁 中国中医科学院眼科医院,北京
陈强 中国中医科学院眼科医院,北京
马群英 中国中医科学院眼科医院,北京
梁丽娜 中国中医科学院眼科医院,北京
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Abstract:
      Objective To develop a murine model of age-related macular degeneration (AMD), using combined chronic exposure to light and hydroquinone, and to characterize the pathological and ultrastructural changes, and retinal function, thus to provide a more suitable model for AMD pathogenesis and treatment research. Methods Twenty 4-monthold C57BL/6 mice were randomly divided into a model group and a normal group, with 10 mice in each. The mice in the model group were fed a diet containing 8 g/ (kg·bw) hydroquinone and received 12 h light exposure daily with an intensity of 2500 lx. Mice in the normal group were fed with the same diet without hydroquinone, and were exposed to conventional illumination. After 3. 5 months, light and electron microscopy and electroretinograms (ERGs) were used to detect structural and functional changes in the retina. Photoreceptor apoptosis was evaluated with TdT-mediated dUTP nick-end labeling (TUNEL) staining, and vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) expression and distribution were detected by immunofluorescence. Results ERGs showed that retinal function of the mice in the model group was lower than that of mice in the normal group. Light microscopy showed atrophic changes in the retinal pigment epithelium (RPE) layer in the model group, and a reduced number of photoreceptor cells (164. 67±34. 37 versus 243. 33±15. 23 in the normal group). There were significantly fewer photoreceptor cells in the model group than in the normal group (t =-9. 77, P <0. 05). Transmission electron microscopy showed that the photoreceptor outer segments of the mice in the model group were loose, deformed and partially fragmented. In addition, the RPE-cell microvilli were shortened; the Bruch’ s membrane became irregularly thickened; and endothelial cells from the choroidal capillary basement membrane penetrated into the Bruch’ s membrane. Apoptosis was rarely found in the normal group. TUNEL staining showed that there were many positive cells in the RPE and photoreceptor layers in the model group. The apoptosis rate was (43±2. 73)% ( P <0. 01). Immunofluorescence showed marked VEGF-positive staining in the RPE layer in the model group, whereas no specific staining was found in the normal group. Immunofluorescence of CD31 showed scattered positive staining in the outer plexiform layer and ganglion cell layer in the normal group, whereas it could also be found in the RPE layer in the model group, which indicated the development of neovascularization. Conclusions The retinas of mice treated with combined hydroquinone and chronic light damage closely mimic the development and characteristics of human AMD, this may provide a reliable animal model for further studies of AMD pathogenesis and management.
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