Loss of TLR4 in mouse Müller cells inhibits both MyD88-dependent and -independent signaling.

Abstract

Müller cells are key to metabolic and ionic regulation in the retina. They also produce a number of inflammatory mediators and are significantly affected in diabetic retinopathy. To investigate the role of toll-like receptor 4 (TLR4) in retinal Müller cells, we crossed TLR4 floxed with PDGFRα-Cre mice to eliminate TLR4 in retinal Müller cells. We performed Western blotting and ELISA analyses to determine whether loss of TLR4 affected myeloid differentiation primary response protein (MyD88)-dependent or -independent signaling, leading to reduced levels of tumor necrosis factor alpha (TNFα) and interleukin 1 beta (IL1β) in whole retinal lysates from the TLR4 floxed and TLR4-PDGFRα-Cre mice. Data show that TLR4-PDGFRα-Cre mice have reduced levels of both the MyD88-dependent and -independent signaling pathways. These studies confirm successful development of a Müller cell-specific TLR4 knockout mouse colony. These mice have reduced MyD88-dependent and -independent signaling pathway proteins, as well as reduced TNFα and IL1β levels. These mice can be used to dissect TLR4 signaling in disorders affecting retinal Müller cells.