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. Experiment Overall Design: We compared the gene expression of retinal pigmental epithelium/choroid from young and old animals. There were 4 samples from young mice and 4 samples from old mice. Each sample contained 4 retinal pigmental epithelium/choroid from 2 animals
Project description:Young mice were compared to old mice (2 month vs 24 month) to determine gene changes that occur with aging in the mouse retinal pigmented epithelium/choroid of the eye. Keywords = retinal pigmented epithelium Keywords = aging Keywords = choroid
Project description:Young mice were compared to old mice (2 month vs 24 month) to determine gene changes that occur with aging in the mouse retinal pigmented epithelium/choroid of the eye. Keywords = retinal pigmented epithelium Keywords = aging Keywords = choroid Keywords: other
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
Project description:Transgenic mice overexpressing human mineralocorticoid receptor (hMR) under the control of the ecologic promotor 1 (P1 hMR mice) were used as well as their WT littermates. We observed anatomical signs of choroid neuropathy in these mice. Bulk-transcriptomic analysis of retinal pigment epithelium/choroid complex was peformed to identify potential mechanisms.
Project description:Purpose To examine how circulating immune mediators in vivo may affect gene and protein expression at the retinal pigment epithelium (RPE)/choroid interface. Methods Young mice were systemically infected with lymphocytic choriomeningitis virus (LCMV) or continuously infused with interferon (IFN)γ. RPE/choroid was isolated and analyzed with whole-transcriptome gene expression microarrays. Selected gene expression findings were validated at the protein level. Results Both the systemic immune activation from virus infection and the sterile systemically increased level of IFNγ resulted in increased expression of chemokine ligands, chemokine receptors and early complement components in isolates of RPE/choroid. These findings were largely absent from LCMV-infected mice deficient in either the interferon α/β receptor or IFNγ. Conclusions Together, these findings demonstrate that acute systemic immune activation results in a local response at the RPE/choroid interface that may include chemokine-dependent recruitment of inflammatory cells and engagement of the complement system. This may represent a link between the systemic low-grade inflammation and the retinal pathology observed in several multifactorial entities such as aging, age-related macular degeneration (AMD) and diabetes.
Project description:Purpose: The complement system is closely linked to the pathogenesis of age-related macular degeneration (AMD). Several complement genes are expressed in retinal pigment epithelium (RPE), and complement proteins accumulate in drusen. Further, a common variant of complement factor H (CFH) confers increased risk of developing AMD. Because the mechanisms by which changes in the function of CFH influence development of AMD are unclear, we examined ocular complement expression as a consequence of age in control and CFH null mutant mice. Methods: Gene expression in neuroretinas and RPE/choroid from young and aged WT and Cfh-/- C57BL/6J mice was analysed by microarrays. Expression of a wide range of complement genes was compared to expression in splenocytes and in liver tissue by qRT-PCR. Results: An age-associated increased expression of complement, particularly C1q, C3 and Factor B, in the RPE/choroid coincided with increased expression of the negative regulators Cfh and Cd59a in the neuroretina. Young mice deficient in CFH expressed Cd59a similar to WT, but failed to upregulate Cd59a expression with age. Both hepatic and splenic expression of Cd59a increased with age regardless of Cfh genotype. Conclusions: While the connection between CFH deficiency and failure to up-regulate CD59a remains unknown, these results suggest that expression of CD59 is tissue-specific and that neuroretinal regulation depends on CFH. This could contribute to the visual functional deficits and morphological changes in the Cfh-/- mouse retina that occur with age, and further suggests that deficient neuroretinal regulation of complement could represent an early event in AMD. Gene expression in neuroretinas and RPE/choroid from young and aged WT and Cfh-/- mice, 4 biological replicates in each group.
Project description:The principal aim of this work was to investigate the methylation profiles of specific ocular tissues, and compare this profile to matched peripheral blood. Matched human blood and eye tissue were obtained post-mortem (n=8) and DNA methylation profiling performed on blood, neurosensory retina, retinal pigment epithelium (RPE)/choroid and optic nerve tissue using the Illumina Infinium HumanMethylation450 platform.