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Miao Tang, Bin Zou, Lai Wei, Heping Xu, Mei Chen; Identification of age-related changes in retinal immune regulatory genes using Single-Cell transcriptomics. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5406.
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To understand the expression profiles of immune regulators in each type of retinal cell and the impact of age on the expression of immune regulatory genes by retinal cells.
Single-Cell RNA sequencing was conducted on retinal tissues from 22-month-old and 3-month-old wild-type C57BL/6J mice using 10X Genomics pipeline. Seurat was used to perform data analysis. The cell-type-dependent expression of various immune regulatory genes, including Cd200, Cd47, Sirpa, Cx3cl1, Cx3cr1, Tgfβ, the endocannabinoids pathway (Cnr1, Dgla, Mgll, Napepld and Faah) and complement related genes, were mapped in young and aged retinas.
A total of 12873 cells were classified into ten types of retinal cells. The cells included rods (58.16%), cones (5.71%), rod bipolar cells (6.79%), cone bipolar cells (17.76%), amacrine cells (6.10%), Müller glia (7.88%), retinal ganglion cells (RGC, 0.40%), horizontal cells (HC, 0.39%), microglia (0.43%) and vascular cells (VC, 0.45%). Retinal microglia expressed high levels of C1q, Trem2, Tyrobp, Sirpa, Cx3cr1, Cfh and C5ar1. With age, the expression of Trem2, Sirpa, and C5ar1 was significantly increased (p< 0.05, Wilcoxon Rank Sum test) and the expression of Cx3cr1 and Cfh decreased, suggesting a low level of activation. Cd200 was highly expressed in VC; whereas Cx3cl1 and genes of the endocannabinoids pathway were expressed predominately in RGC. A reduction in the expression of Cx3cl1, Napepld and Faah was observed in RGC from aged retina. Among various complement related genes, the expression of complement inhibitors (Cfh, Crry, Cd59a, Serping1, CD46) was generally higher than that of complement activators (C1ra, C2, C4b, Masp2) in retinal cells. The inhibitors were expressed by VC, microglia, RGC, HC and photoreceptors; whereas the activators were expressed predominately by Müller glia and HC. With age, the expression of Cfh decreased, whereas the expression of CD59a and Serping1 increased in VC.
Retinal vascular cells and neurons, including RGC, HC and photoreceptors, express a variety of immune regulatory genes. These immune regulators may critically control retinal microglial and complement activation under normal physiological conditions. The age-related reduction in the expression of the immune regulators such as Cx3cl1 and Cfh may explain the low-grade para-inflammation in the aging retina previously reported by us and others.
This is a 2020 ARVO Annual Meeting abstract.
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