Loss of TLR4 in endothelial cells but not Müller cells protects the diabetic retina. (May 2021)

• Record Type: Journal Article
• Authors: Seidel, Adam; Liu, Li; Jiang, Youde; Steinle, Jena J.
• Is Part Of: Experimental eye research. Volume 206(2021)
• Publication Date: 2021-05
• Subjects: Toll-like receptor 4 -- Diabetic retinopathy -- Endothelial cells -- Müller cells; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2021.108557
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Others have previously reported that global loss of toll-like receptor 4 (TLR4) reduced retinal inflammation. To determine cell specific actions of TLR4 in the retina, we generated diabetic endothelial cell specific and Müller cell specific TLR4 knockout mice. Diabetic Cdh5-Cre TLR4 mice, PDGFRα-Cre TLR4 mice, and TLR4 floxed mice were evaluated for retinal permeability, neuronal damage, and numbers of degenerate capillaries, all changes commonly observed in the diabetic retina. We also measured protein levels of key inflammatory mediators. We found that diabetes increased permeability, neuronal, and vascular damage in all mice. Loss of TLR4 in the retinal endothelial cells protected against these changes when compared to diabetic TLR4 floxed mice. In contrast, loss of TLR4 in Müller cells did not reduce diabetes-induced increases in permeability or neuronal and vascular damage. Elimination of TLR4 in either mouse model reduced inflammatory mediators, as well as VEGF levels. Taken together, our findings suggest that loss of TLR4 in endothelial cells is protective against diabetic-induced damage, while Müller cell TLR4 is not involved in the damage. Highlights: -Diabetic cdh5-Cre TLR4 and PDGFRα-Cre TLR4 mice were used investigate endothelial cell specific and Müller cell specific TLR4 actions, respectively. -Loss of TLR4 in endothelial cells protected against diabetes-induced damage, while loss of TLR4 in Muller cells was not protective.