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Yoko Okunuki, Garrett Klokman, Kip M Connor; miR-155 regulates microglia activation in a murine model of retinal detachment. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5967. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Degeneration of photoreceptors, a primary cause of vision loss worldwide, is caused by a wide range of retinal pathologies, including retinal detachment (RD). Understanding the underlying mechanisms surrounding photoreceptor cell death is critical to developing new treatment strategies. Since photoreceptors are non-dividing cells, their loss leads to irreversible visual impairment, even after successful retinal reattachment surgery. Currently, our knowledge of the processes for which photoreceptors degenerate is very poorly understood. Retinal microglia become activated during RD however, the role of microglia in the pathophysiology of photoreceptor cell death is not well understood. The association of pro-inflammatory microRNA-155 (miR-155), abundantly expressed in microglia, is suggested to be associated with worsening of neurodegenerative brain diseases. In this study, we examined the role of miR-155 on photoreceptor cell death in RD.
RD was induced by subretinal injection of 4 μl of sodium hyaluronate in miR-155 -/- mice and C57BL/6J mice. RD-induced photoreceptor cell death was compared between miR-155 -/- mice and C57BL/6J mice by TUNEL staining. Microglia were isolated from intact retinas and 24hr post RD retinas of C57BL/6J mice by fluorescence-activated cell sorting, and miR-155 expression in microglia was measured by RT-PCR.
The number of TUNEL positive cells in miR-155 -/- retinas was significantly decreased 24hrs after RD (p=0.008, n=8). Microglial miR-155 expression was significantly increased in 24hr post RD retinas compared to intact retinas (p<0.001).
Loss of miR-155 suppressed photoreceptor cell death in response to RD. Moreover, miR-155 expression was significantly induced in retinal microglia in response to RD. Preliminary data suggests that miR-155 loss protects photoreceptor cells from cell death, although the exact role of microglial expression of miR-155 with retinal damage still needs further elucidation.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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