Inositol (1,4,5)-trisphosphate 5-phosphatase promotes survival of uveal melanoma by regulating oncogenic G protein-driven calcium oscillations.

Mutant constitutively active (CA) G protein α-subunits encoded by GNAQ or GNA11 (CA-GNAQ/11) drive uveal melanoma (UM), occur in uncommon subtypes of other cancers, and cause Sturge-Weber syndrome and other capillary malformations. CA-GNAQ/11 activates phospholipase Cβ, which cleaves phosphatidylinositol (4,5)-bisphosphate at high rate to produce diacylglycerol that drives oncogenesis and inositol (1,4,5)-trisphosphate (IP3) that releases Ca from intracellular stores and triggers store-operated Ca entry. For poorly understood reasons, high IP3 flux in UM cells does not elicit Ca overload and death.

Risk Factors for Macular Hole Development After Pars Plana Vitrectomy for Rhegmatogenous Retinal Detachment.

To identify intraoperative and postoperative risk factors for macular hole (MH) formation after prior pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) repair. This retrospective case-control study compared eyes that developed MH after PPV for RRD (cases) and those that underwent PPV for RRD without forming MH (controls). Cases were matched to controls using propensity scores based on demographic, preoperative, and RRD characteristics.

Early Genetic Evolution of Driver Mutations in Uveal Melanoma.

Uveal melanoma (UM) is an aggressive cancer of the eye that frequently results in metastatic death. UMs are most likely to metastasize when they are small, at a time when they are difficult to distinguish from benign nevi and often observed without treatment. Unfortunately, little is known about the early genetic evolution of UM or potential biomarkers to indicate small tumors undergoing malignant transformation.

15-Gene Expression Profile and as Integrated Prognostic Test for Uveal Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1).

PURPOSEValidated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/ classifier.MATERIALS AND METHODSThis study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers.

Vitreous microparticles contain apoptotic signals suggesting a diabetic vitreopathy.

Aim: To evaluate differences in microparticle profiles in vitreous samples between diabetic and non-diabetic eyes undergoing vitrectomy.

Methods: Un-masked cross-sectional series of 34 eyes undergoing vitrectomy. Vitreous specimens were collected and processed to evaluate for membrane integrity (DAPI), apoptosis (Annexin-V), and endothelial-cell origin (V-Cadherin).

Oncogenic Gq/11 signaling acutely drives and chronically sustains metabolic reprogramming in uveal melanoma.

Metabolic reprogramming has been shown to occur in uveal melanoma (UM), the most common intraocular tumor in adults. Mechanisms driving metabolic reprogramming in UM are poorly understood. Elucidation of these mechanisms could inform development of new therapeutic strategies for metastatic UM, which has poor prognosis because existing therapies are ineffective.

Targeting primary and metastatic uveal melanoma with a G protein inhibitor.

Uveal melanoma (UM) is the most common intraocular tumor in adults. Nearly half of UM patients develop metastatic disease and often succumb within months because effective therapy is lacking. A novel therapeutic approach has been suggested by the discovery that UM cell lines driven by mutant constitutively active Gq or G11 can be targeted by FR900359 (FR) or YM-254890, which are bioavailable, selective inhibitors of the Gq/11/14 subfamily of heterotrimeric G proteins.

Anterior Chamber Angles after Intravitreal Injections for Macular Degeneration.

The mechanism underlying IOP elevation associated with intravitreal injections is unknown. Using anterior segment OCT, we found no significant differences in angle width associated with number of intravitreal injections that might explain this phenomenon.

TLR-mediated induction of negative regulatory ligands on dendritic cells.

Dendritic cells (DCs) shape T-cell response patterns and determine early, intermediate, and late outcomes of immune recognition events. They either facilitate immunostimulation or induce tolerance, possibly determined by initial DC activation signals, such as binding Toll-like receptor (TLR) ligands. Here, we report that DC stimulation through the TLR3 ligand dsRNA [poly(I:C)] limits CD4 T-cell proliferation, curtailing adaptive immune responses.