RGS2-deficient mice exhibit decreased intraocular pressure and increased retinal ganglion cell survival.

Purpose: Contractile activity of the trabecular meshwork (TM) and ciliary muscle (CM) influences aqueous humor drainage; however, the mechanisms linking tissue contractility and regulation of aqueous humor drainage are not well understood. Regulator of G Protein Signaling 2 (RGS2), a GTPase-activating protein of the Galphaq family of proteins, plays a critical role in regulation of contractile activity of vascular smooth muscle and in blood pressure homeostasis. To explore a potential role for RGS2 in intraocular pressure (IOP) homeostasis, we evaluated RGS2 knockout (RGS2(-/-)) mice for changes in IOP.

Methods: IOP was measured using a rebound tonometer in awake male RGS2(-/-) and littermate wild-type mice. Histological and immunofluorescence analyses were performed to evaluate changes in the iridocorneal structure, actomyosin organization in CM and TM, and retinal ganglion cell survival in both central and peripheral retina.

Results: In repeated measurements, IOP was found to be consistently lower in the RGS2(-/-) mice compared to littermate wild-type mice. This change in IOP appears to be associated with increased actin filament assembly in the CM, and widening of the Schlemm's canal in the aqueous humor drainage pathway. Furthermore, ganglion cell number in the central retina was found to be significantly higher in the RGS2(-/-) mice relative to wild-type mice.

Conclusions: The data suggest that the deficiency of RGS2 decreased IOP, presumably due to increased aqueous humor drainage in association with increased CM contraction. These data indicate a potentially critical role for RGS2 in homeostasis of IOP and for retinal ganglion cell survival.