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M. M. Inoue, T. Inoue, D. L. Epstein, K. J. Blumer, P. V. Rao; Intraocular Pressure (IOP) Changes in RGS-2 (Regulator of G-Protein Signaling) Null Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1637.
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To explore the cellular mechanisms regulating IOP and aqueous humor outflow through the trabecular meshwork, we evaluated IOP changes in a mouse model with a homozygous deletion of RGS-2, the negative regulator of the G-protein coupled receptor, Gαq. Gαq is one of the predominant G-proteins involved in regulation of contractile properties of both smooth muscle and non-muscle tissues. The RGS-2 null mice have been reported to develop severe systemic hypertension because of increased vascular endothelial constriction.
Expression of RGS-2 in the trabecular meshwork and ciliary muscle cells were determined by RT-PCR. IOP measurements were carried-out in RGS-2 null and wild type mice using a rebound tonometer under the awake condition. The cryosections of the eye anterior segments were stained for actin filament with rhodamin phalloidin. To examine the changes in retinal ganglion cell (RGC) survival, we immunostained the RGC cells with Brn3 antibody in retinal cryosections obtained from the RGS-2 null and wild type mice.
Both human TM and ciliary muscle cells were confirmed to express RGS-2 and Gαq. The RGS-2 null mice compared to their respective wild type mice showed decreased IOP in repeated evaluation. The trabecular meshwork of the RGS-2 null mice exhibited increased actin filament staining compared to that of wild type specimens. The number of RGCs in the central retina was significantly higher in RGS-2 null mice compared to that of wild type mice.
This study demonstrates the importance of RGS-2 in the regulation of IOP and the lack of RGS-2 expression is associated with a lower IOP in a mouse model. This work offers an important insight into the homeostasis of IOP by the Gαq-associated G-protein coupled receptors. Moreover, our data also indicate an enhanced RGC survival in RGS-2 null mice. Whether this relates to the observed lower IOP or some other non-IOP associated mechanics of IOP requires further studies.
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