TLR4 deficiency does not alter glaucomatous progression in a mouse model of chronic glaucoma.

Abstract

Glaucoma is a leading cause of irreversible blindness worldwide. Toll-like receptor 4 (TLR4) is a pattern-recognition transmembrane receptor that induces neuroinflammatory processes in response to injury. Tlr4 is highly expressed in ocular tissues and is known to modulate inflammatory processes in both anterior and posterior segment tissues. TLR4 activation can lead to mitochondrial dysfunction and metabolic deficits in inflammatory disorders. Due to its effects on inflammation and metabolism, TLR4 is a candidate to participate in glaucoma pathogenesis. It has been suggested as a therapeutic target based on studies using acute models, such as experimentally raising IOP to ischemia-inducing levels. Nevertheless, its role in chronic glaucoma needs further evaluation. In the current study, we investigated the role of TLR4 in an inherited mouse model of chronic glaucoma, DBA/2J. To do this, we analyzed the effect of Tlr4 knockout (Tlr4) on glaucoma in DBA/2J mice. Our studies found no significant differences in intraocular pressure, iris disease, or glaucomatous progression in Tlr4compared to Tlr4DBA/2J mice. Our data do not support a role for TLR4 as a treatment target in chronic glaucoma.