We discovered a protective role of G protein-coupled receptor 3 (GPR3) in a mouse model of T cell-mediated autoimmune uveitis. GPR3 is an orphan receptor that maintains Gs-coupling and cyclic AMP production without an exogenous ligand. Consequently, GPR3 deficient (GPR3KO) mice were more susceptible to developing experimental autoimmune uveitis (EAU) induced by immunization with interphotoreceptor retinoid-binding protein (IRBP) or by adoptive transfer of IRBP-specific T cells than their wild type (WT) littermates. T cells isolated from IRBP-immunized GPR3KO mice demonstrated an increase in proliferation and inflammatory cytokine production in response to the specific IRBP antigen and a relatively high resistance to activation-induced T cell death compared to T cells isolated from immunized WT mice. Moreover, a major tight junction protein such as ZO-1 was reduced in GPR3 deficient retina with severe uveitis after IRBP-specific T cells were transferred. Taken together, our findings suggest that constitutively active GPR3 inhibits T cell mediated retinal inflammation.

Ocular trauma and surgery are considered the most common cause for proliferative vitreoretinopathy (PVR). Many retinal cell types are thought to be the cellular source for PVR although most risk factors for PVR are associated with intravitreal dispersion of the retinal pigment epithelium (RPE) cells. Major PVR animal models are rabbit and swine with an artificial implantation of exogenous cells into the vitreous to form epiretinal membrane (ERM) which does not recapitulate a real PVR pathology. To clarify and validate the participation of RPE cells, to mimic ocular trauma in situ, and to reveal the related macromolecule changes in PVR pathology, we utilized a dispase treatment to damage the retina in establishment of a reliable RPE-tagged PVR mouse model with ERM-like tissues formed within and on both surface of the retina. The immunostaining of patient epiretinal membranes with lineage markers confirms RPE is involved in PVR development. Quantitative PCR analysis indicates the dedifferentiation of RPE cells switches RPE from epithelial to mesenchymal phenotype to re-enter a proliferative and mobile state underlying PVR. Gene expression results of the mouse PVR model retinas are consistent with the microarray gene expression profile of human PVR retinas, validating that our mouse PVR model resembles human PVR and is thereby suitable for molecular mechanism and pharmaceutical studies.

The purpose of this study was to evaluate the impact of vitrectomy and posterior hyaloid (PH) peeling on color alteration of optic nerve head (ONH) and retina as a surrogate biomarker of induced perfusion changes.

Short chain fatty acids (SCFAs) produced by gut microbiota are known to play primary roles in gut homeostasis by immunomodulation partially through G-protein coupled receptors (GPR) 43. Using mouse models of TLR ligand induced keratitis, we investigated whether SCFAs and GPR43 play any regulatory roles in the pathogenesis of inflammatory responses in the eye.