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Bing Xu Ross, Jingyu Yao, Sumathi Shanmugam, Steven F Abcouwer, David N. Zacks; Retinal Detachment Triggers an Innate Immune Response in the Retina. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4964. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Retinal detachment (RD) disrupts the nutritional support for photoreceptors (PRs) from the underlying retinal pigment epithelium, eventually causing PR cell death and vision loss. RD activates the intra-retinal innate immune response; however, a considerable knowledge gap exists regarding the role this plays in determining PR cell fate. The purpose of this study was to characterize the innate immune response following RD.
Methods: C57BL/6 mice were sub-retinally injected with 1% hyaluronic acid to create an acute RD model. Retinal RNA was isolated at 1, 2, 3, and 7 days post RD (dprd) and quantitative RT-PCR analysis was used to evaluate the mRNA levels of IL-1β, monocyte chemoattractant protein 1 (MCP-1/CCL2), interferon gamma-induced protein 10 (IP-10/CXCL10), IL-10, Toll-like receptor (TLR) 2 and TLR4. Western blotting was used to examine the effects of RD on TLR2 protein expression. Immunofluorescence with an antibody to ionized calcium-binding adapter molecule 1 (Iba1) was used to evaluate the mobilization of microglia/macrophages following RD.
Results: RD resulted in a rapid and marked increase of the innate immune and major inflammatory mediator IL-1β (49.6-fold increase, p<0.001), and the monocyte chemokine MCP-1/CCL2 (561.7-fold increase, p<0.001), with their enhanced expression sustained till 7 dprd. In addition, the chemokine CXCL10 expression showed significant upregulation at 7 dprd (4.2-fold increase, p<0.05). Yet RD dampened the expression of the anti-inflammatory cytokine IL-10 at 2 dprd (0.4-fold decrease, p<0.05). Meanwhile, the innate immune receptor TLR2 was promptly elevated at 1 dprd (10.1-fold increase, p<0.01) and remained elevated at 7 dprd, while TLR4 mRNA remained at baseline level after RD. We further detected significant increase of TLR2 proteins at 2, 3, and 7 dprd. Iba1-positive cells migrated to the outer nuclear layer and the inner and outer segment of PRs at 3 dprd, with a greater abundance in the inner and outer segment area at 7 dprd.
Conclusions: RD triggers the expression of pro-inflammatory cytokines and chemokines, increases TLR2 expression, dampens IL-10 expression, and is associated with the migration and infiltration of microglia/macrophages to the stressed PR area. Modifying the innate immune response to minimize detrimental inflammation may improve PR survival after RD and provide therapeutic insights to other inflammatory eye diseases.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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