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Keynote: J Clin Exp Ophthalmol 2013
Although the mouse has no macula leutea, its neuroretina and retinal pigment epithelium can develop lesions mimicking certain features of age-related macular degeneration (AMD). Differences between Ccl2 and Cx3cr1 double deficient mouse on rd8 background (DKO rd8 ) and Crb1 rd8 photoreceptor and RPE pathology, as well as increased A2E and immune dysfunction, show that DKO rd8 recapitulates some human AMD-like features in addition to rd8 retinal dystrophy/degeneration. Different therapeutic interventions have been demonstrated effective on the AMD-like features of DKO rd8 mice. The use of the DKO rd8 model and C57BL/6N (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 the DKO rd8 mice as self-control 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. Two examples will be presented: (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 sFLT101 (AAV5.sFLT101) stabilizes the AMD-like lesions via lowering retinal extracellular signal- regulated kinase (ERK) phosphorylation and iNOS expression. Therefore, the DKO rd8 mouse model can be useful and appropriate for therapeutic compound screening in the management of human AMD.
Chi-Chao Chan earned her M.D. from Johns Hopkins University and ophthalmology residency from Stanford University School of Medicine. She has completed two post-doctoral fellowships: Ophthalmic Pathology at Wilmer Institute, Johns Hopkins and clinical ocular immunology at National Eye Institute, National Institutes of Health. Dr. Chan is the Chief of Immunopathology Section, Laboratory of Immunology and Head of Histopathology Core, National Eye Institute, the federal government medical research institute in the US. She has published 579 papers in peer-reviewed journals and one textbook. She also serves as an Editorial Board Member for 15 medical journals.