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Sumiko Watanabe, Hideto Koso; Identification of microglia specific genes using a new mouse model of rod photoreceptor degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2238.
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© ARVO (1962-2015); The Authors (2016-present)
Microglia are macrophage-like cells, but constitutive resident in brain and retina. Retinal degeneration and injury induce microglial activation. At the same time, infiltration of monocyte-derived macrophages into the retina was reported, suggesting coexistence of these cells within the same lesion. However, their difference in function and features in retinal degeneration remain elusive. We aimed to clarify molecular events involving microglia and macrophage during progression of retinal degeneration.
We generated a genetic mouse model of rod photoreceptor degeneration in which rod was injured by rod-photoreceptor specific expression of Diphtheria toxin fragment A (DTA). The expression of DTA was induced by administration of tamoxifen to the mice, thereby we can analyze early stage of rod degeneration using this mice. To distinguish microglia and macrophage, we performed bone marrow transplantation (BMT) by using the EGFP-expressing mouse as a donor. Cellular phenotype was examined by immunostaining, and microarray and RNAseq were done to investigate molecular events.
Rod photoreceptor degeneration was induced by administration of tamoxifen, and Mueller glia followed by microglia activation was observed. Large number of genes was induced one day after the onset of rod degeneration, and ontology analysis identified enrichment of immune-response related genes in the induced genes. BMT showed differential spatial distribution of microglia and macrophage in the retina, suggesting different roles of these two types of cells in the injured retina. Microglia or macrophage specific genes were identified by RNAseq using purified microglia and macrophages. Functional analysis of one of the microglia specific genes revealed its roles in maturation of microglia in both retina and brain.
A newly established mouse model of rod photoreceptor degeneration revealed transition of cellular and molecular events after onset of rod degeneration. Number of genes specifically expressed/induced in microglia or macrophages were identified, allowing us to regulate immune-related cellular events during photoreceptor degeneration through modulation of these gene expression.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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