Toll-like receptor 4 regulates insulin signal transduction in retinal Muller cells

Dysfunctional insulin signalling is a causative factor in type-2 diabetes. While insulin signal transduction has been well investigated in many tissues, less is known in retinal tissues. We have previously reported that toll-like receptor 4 (TLR4) is involved in retinal damage in diabetes. We used TLR4 retinal Muller cell-specific knockout mice and Muller cells in culture to investigate the effects of loss of TLR4 on Muller cell insulin signal transduction. Loss of TLR4 in the mouse retinal Muller cells led to increased insulin receptor and Akt phosphorylation, with reduced insulin receptor substrate 1 (IRS-1) phosphorylation on serine 307, which was associated with reduced cleavage of caspase 3. In retinal Muller cells grown in high glucose, insulin signal transduction was impaired, but these responses were reduced with cells were transfected with TLR4 siRNA. Taken together, the data suggest that TLR4 regulates insulin signal transduction in retinal Muller cells.