Project description:Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. There are two types of AMD: dry AMD and wet AMD. While laser-induced choroidal neovascularization has been used extensively in the studies of wet AMD by presenting the main features of human wet AMD, there was no established mouse model which fully recapitulates the cardinal features of human dry AMD. In this regard, lack of appropriate mouse model for dry AMD hampered the translational research on the pathogenesis and development of therapeutic agents. We recently suggested that 5XFAD mice could be a mouse model of dry AMD with regard to the amyloid beta (Aβ) related pathology. In this study, using transmission electron microscope, we analyzed ultrastructure of retinal pigment epithelium (RPE) of 5XFAD mice. Of importance, aged 5XFAD mice had ultrastructural changes of RPE and Bruchâs membrane compatible with cardinal features of dry AMD, including loss of apical microvilli and basal infolding of RPE, increased thickness of Bruchâs membrane, basal laminar and linear deposits, and accumulation of lipofuscin granules and undigested photoreceptor outer segment-laiden phagosomes. Using a threshold of 1.2 fold difference, we found â564â differentially expressed genes of which â190â were up-regulated and â374â were down-regulated in the RPE complex of aged 5XFAD mice. These altered genes were implicated in the pathogenesis of AMD including inflammation and immune response-related genes and retinol metabolism-related genes. Taken together, we suggest that aged 5XFAD mice can be used for dry AMD mouse model. All 5XFAD mice used were heterozygotes with respect to the transgene, and non-transgenic wild-type littermate (WT) mice served as controls.
Project description:Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. There are two types of AMD: dry AMD and wet AMD. While laser-induced choroidal neovascularization has been used extensively in the studies of wet AMD by presenting the main features of human wet AMD, there was no established mouse model which fully recapitulates the cardinal features of human dry AMD. In this regard, lack of appropriate mouse model for dry AMD hampered the translational research on the pathogenesis and development of therapeutic agents. We recently suggested that 5XFAD mice could be a mouse model of dry AMD with regard to the amyloid beta (Aβ) related pathology. In this study, using transmission electron microscope, we analyzed ultrastructure of retinal pigment epithelium (RPE) of 5XFAD mice. Of importance, aged 5XFAD mice had ultrastructural changes of RPE and Bruch’s membrane compatible with cardinal features of dry AMD, including loss of apical microvilli and basal infolding of RPE, increased thickness of Bruch’s membrane, basal laminar and linear deposits, and accumulation of lipofuscin granules and undigested photoreceptor outer segment-laiden phagosomes. Using a threshold of 1.2 fold difference, we found “564” differentially expressed genes of which “190” were up-regulated and “374” were down-regulated in the RPE complex of aged 5XFAD mice. These altered genes were implicated in the pathogenesis of AMD including inflammation and immune response-related genes and retinol metabolism-related genes. Taken together, we suggest that aged 5XFAD mice can be used for dry AMD mouse model.
Project description:Age-related macular degeneration (AMD) is a leading cause of vision loss, with its dry form characterized by retinal pigment epithelium (RPE) degeneration and photoreceptor loss. However, the underlying mechanisms driving these pathological changes remain poorly understood. Here, we identify a critical role for microglia-RPE cell interactions mediated by the SPP1-ITGAV signaling axis in dry AMD pathogenesis.
Project description:Macrophage aging is pathogenic in numerous age-associated diseases, including age-related macular degeneration. The purpose of this experiment was to profile microRNA expression in young and aged macrophages at baseline and in response to oxLDL and acLDL.
Project description:To characterize underlying changes in the retinal pigment epithelium (RPE)/choroid with age, we produced gene expression profiles for the RPE/choroid and compared the transcriptional profiles of the RPE/choroid from young and old mice. The changes in the aged RPE/choroid suggest that the tissue has become immunologically active. Such phenotypic changes in the normal aged RPE/choroid may provide a background for the development of age-related macular degeneration. Keywords: age-related change
2008-03-29 | GSE10965 | GEO
Project description:GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology