Purchase this article with an account.
Stephen Rasiah, Tiffany Wang, Bongsu Kim, Amanda Bingham, Mohamed H. Abdel-Rahman, Andy J. Fischer, Colleen M. Cebulla; Macrophage Polarization In Experimental Murine Retinal Detachment. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4265.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Alternately activated M2 macrophages are a source of cytokines that play a role in many pro-fibrotic diseases. It is unknown whether macrophage polarization could play a role in the development of proliferative vitreoretinopathy (PVR) following retinal detachment. The purpose of this study was to evaluate macrophage accumulation and gene expression in a murine model of retinal detachment.
Retinal detachments were created in the left eyes of (22-24 week-old) C57BL/6 mice (untreated right eyes served as controls). For gene expression studies, short-term and long-term RDs were created with subretinal injection of saline or hyaluronic acid (HA, 10mg/ml), respectively. Mouse retinas (n=5 per group) were isolated at each timepoint (day 1, week 1, week 2, week 5) and expression of various monocyte-associated (Mcp1), M1 (Cxcl10, Nos2), and M2 (Mrc1, Retnla, Chi3l1, IL13) genes was evaluated with qPCR. GAPDH was used as a control. Immunohistochemical studies were performed to evaluate macrophage/microglia expression, with Iba-1 and F4/80 markers, and fibrosis, with GFAP, in the detached retina in 2wk and 4wk RDs. The percentage of macrophages with the M2 phenotype was determined in 2 wk and 4 wk RDs. The percentage of CD163 positive (M2) macrophages to total F4/80+ macrophages was determined using dual labeling techniques.
RD retinas exhibited a strong, sustained up-regulation of Mcp1 gene expression at all timepoints (range 16-98 fold increase) in both saline and HA RDs. The M1-related gene Cxcl10 was increased at all timepoints except week 5, while Nos2 expression was not significantly increased. Some M2-related genes were strongly up-regulated including Mrc1 and Retnla. Chi3l1 and IL13 expression were modestly increased. Immunohistochemistry demonstrated local accumulations of retinal and subretinal macrophages/microglia in the detached retina, particularly in areas of up-regulated GFAP and subretinal scar, compared to controls. CD163 positive macrophages represented 29% of total macrophages.
There is a focal inflammatory response in retinal detachment with an M2 macrophage presence and M2-associated gene expression seen in the murine retinal detachment model. Macrophages may contribute to the development of retinal fibrosis in RD.
This PDF is available to Subscribers Only