title: Evaluating Potential Therapies in a Mouse Model of Focal Retinal Degeneration with Age-related Macular Degeneration (AMD)-Like Lesions.
abstract: 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 theCcl2andCx3cr1double deficient mouse onCrb1rd8(rd8) background (DKOrd8) and theCrb1rd8mouse in photoreceptor and RPE pathology, as well as ocularA2E contents and immune responses, show that DKOrd8recapitulates some human AMD-like features in addition tord8retinal dystrophy/degeneration. Different therapeutic interventions have been demonstrated to be effective on the AMD-like features of DKOrd8mice. The use of the DKOrd8model 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 DKOrd8mouse 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 factor-inducible 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 DKOrd8mouse model can be useful and appropriate for therapeutic compound screening in the management of human AMD.
authors.affiliation: Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Dr., 10/10N103, NIH/NEI, Bethesda, MD, 20892-1857, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Popp
authors.affiliation: Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Dr., 10/10N103, NIH/NEI, Bethesda, MD, 20892-1857, USA.
authors.forename: Xi K
authors.initials: XK
authors.lastname: Chu
authors.affiliation: Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Dr., 10/10N103, NIH/NEI, Bethesda, MD, 20892-1857, USA.
authors.forename: Defen
authors.initials: D
authors.lastname: Shen
authors.affiliation: Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Dr., 10/10N103, NIH/NEI, Bethesda, MD, 20892-1857, USA.
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Tuo
authors.affiliation: Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Dr., 10/10N103, NIH/NEI, Bethesda, MD, 20892-1857, USA.
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
keywords: Age-related macular degeneration (AMD); Ccl2; Cx3cr1; Mouse models; Therapy; rd8