Evaluating Potential Therapies in a Mouse Model of Focal Retinal Degeneration with Age-related Macular Degeneration (AMD)-Like Lesions
|Nicholas Popp, Xi K. Chu, Defen Shen, Jingsheng Tuo and Chi-Chao Chan*|
|Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Dr., 10/10N103, NIH/NEI, Bethesda, MD, 20892- 1857, USA|
|Corresponding Author :||Chi-Chao Chan
Senior Investigator, Immunopathology Section
Laboratory of Immunology, National Eye Institute
National Institutes of Health, 10 Center Dr.
10/10N103, NIH/NEI, Bethesda, MD, 20892-1857, USA
E-mail: [email protected]
|Received July 10, 2013; Accepted September 16, 2013; Published September 23, 2013|
|Citation: Popp N, Chu XK, Shen D, Tuo J, Chan CC (2013) Evaluating Potential Therapies in a Mouse Model of Focal Retinal Degeneration with Age-related Macular Degeneration (AMD)-Like Lesions. J Clin Exp Ophthalmol 4:296. doi:10.4172/2155-9570.1000296|
|Copyright: © 2013 Popp N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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Although the mouse has no macula leutea, its neuroretina and retinal pigment epithelium (RPE) can develop lesions mimicking certain features of age-related macular degeneration (AMD). Differences between the Ccl2 and Cx3cr1 double deficient mouse on Crb1rd8(rd8) background (DKOrd8) and the Crb1rd8 mouse in photoreceptor and RPE pathology, as well as ocularA2E contents and immune responses, show that DKOrd8 recapitulates some human AMD-like features in addition to rd8 retinal dystrophy/degeneration. Different therapeutic interventions have been demonstrated to be effective on the AMD-like features of DKOrd8 mice. The use of the DKOrd8 model and C57BL/6N (wild type, WT) mice as group controls (4 groups) to test treatments such as high omega-3 polyunsaturated fatty acid (n-3) diet has, for example, shown the beneficial effect of n-3 on AMD-like lesions by anti-inflammatory action of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The use of self-control in the DKOrd8 mouse by treating one eye and using the contralateral eye as the control for the same mouse allows for appropriate interventional experiments and evaluates various novel therapeutic agents. Three examples will be briefly presented and discussed: (1) tumor necrosis factorinducible gene 6 recombinant protein (TSG-6) arrests the AMD-like lesions via modulation of ocular immunological gene expression, e.g., Il-17a; (2) adeno-associated virus encoding sIL-17R (AAV2.sIL17R) stabilizes the AMD-like lesions; and (3) pigment epithelium-derived factor (PEDF) ameliorates the AMD-lesions by its anti-inflammatory, anti-apoptotic and neuroprotective roles. Therefore, the DKOrd8 mouse model can be useful and appropriate for therapeutic compound screening in the management of human AMD.