Retinal Vascular Abnormalities and Microglia Activation in Mice with Deficiency in Cytochrome P450 46A1-Mediated Cholesterol Removal.

CYP46A1 is the cytochrome P450 enzyme that converts cholesterol to 24-hydroxycholesterol, a cholesterol elimination product and a potent liver X receptor (LXR) ligand. We conducted retinal characterizations of Cyp46a1 mice that had normal fasting blood glucose levels but up to a 1.8-fold increase in retinal cholesterol.

Correlation of ultra-widefield fundus autofluorescence patterns with the underlying genotype in retinal dystrophies and retinitis pigmentosa.

Purpose: Ultra-widefield fundus autofluorescence (UW-FAF) allows the characterization of the peripheral retinal features of vitreoretinal diseases. The purpose of this study was to examine possible genotypic/phenotypic correlations of UW-FAF patterns in patients with a variety of retinal dystrophies and retinitis pigmentosa (RP).

Methods: An IRB-approved retrospective consecutive case series study was performed of genetically characterized retinal dystrophy or RP patients who underwent UW-FAF imaging.

Ultra-widefield fundus autofluorescence patterns in retinitis pigmentosa and other retinal dystrophies.

Ultra-widefield fundus autofluorescence (UW-FAF) allows for the characterization of the peripheral retinal features of vitreoretinal diseases. The purpose of this study was to examine possible genotypic/phenotypic correlations of UW-FAF patterns in patients with a variety of retinal dystrophies and retinitis pigmentosa (RP). Seventeen patients were identified who had identified mutations in retinal dystrophy or RP genes and who also had undergone UW-FAF.

Wound construction.

Wound construction is critical in microincision vitrectomy surgery. The three main steps in constructing a proper wound include displacing the conjunctiva away from the sclera, flattening the sclera on insertion, and angling the incision. Each one of these steps helps create wounds that will not leak.

Aflibercept for the treatment of age-related macular degeneration.

Aflibercept is a novel, recombinant, fusion protein that consists of portions of vascular endothelial growth factor (VEGF) receptor (R) 1 and VEGFR2 extracellular domains fused to the Fc portion of human immunoglobulin G1. It exhibits higher affinity for VEGF-A/-B and binds all the VEGF isoforms (VEGF-B and -C, placental growth factor). The efficacy of aflibercept was assessed in two randomized, double-masked, multicenter, active-controlled, clinical trials in patients with choroidal neovascularization due to exudative age-related macular degeneration (AMD) and compared it's efficacy to ranibizumab, which is already Food and Drug Administration (FDA)-approved for patients with wet AMD.

Optical coherence tomography imaging of macular oedema.

Macular oedema (ME) occurs in a wide variety of pathological conditions and accounts for different degrees of vision loss. Early detection of ME is therefore critical for diagnosis and therapeutic management. Optical coherence tomography (OCT) is a non-contact, diagnostic method that uses infrared light, which allows the analysis of the retinal structure by means of high-resolution tomographic cross sections.

Inducing a visceral organ to protect a peripheral capillary bed: stabilizing hepatic HIF-1α prevents oxygen-induced retinopathy.

Activation of hypoxia-inducible factor (HIF) can prevent oxygen-induced retinopathy in rodents. Here we demonstrate that dimethyloxaloylglycine (DMOG)-induced retinovascular protection is dependent on hepatic HIF-1 because mice deficient in liver-specific HIF-1α experience hyperoxia-induced damage even with DMOG treatment, whereas DMOG-treated wild-type mice have 50% less avascular retina (P < 0.0001).

Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy in the rat 50/10 model.

Purpose: To study the effect of systemic hypoxia-inducible factor prolyl hydroxylase inhibition (HIF PHDi) in the rat 50/10 oxygen-induced retinopathy (OIR) model.

Methods: Oxygen-induced retinopathy was created with the rat 50/10 OIR model. OIR animals received intraperitoneal injections of dimethyloxalylglycine (DMOG, 200 μg/g), an antagonist of α-ketoglutarate cofactor and inhibitor for HIF PHD, on postnatal day (P)3, P5, and P7.

AMP-activated protein kinase suppresses matrix metalloproteinase-9 expression in mouse embryonic fibroblasts.

Matrix metalloproteinase-9 (MMP-9) plays a critical role in tissue remodeling under both physiological and pathological conditions. Although MMP-9 expression is low in most cells and is tightly controlled, the mechanism of its regulation is poorly understood. We utilized mouse embryonic fibroblasts (MEFs) that were nullizygous for the catalytic α subunit of AMP-activated protein kinase (AMPK), which is a key regulator of energy homeostasis, to identify AMPK as a suppressor of MMP-9 expression.

In vivo evaluation of laser-induced choroidal neovascularization using spectral-domain optical coherence tomography.

Purpose: To describe the in vivo evolution of laser-induced choroidal neovascularization (CNV) in mice using spectral domain optical coherence tomography (SD-OCT).

Methods: Laser photocoagulation was applied to the mouse fundus using a 532-nm diode laser (100, 150, and 200 mW; 100-μm diameter, 0.1-second duration).

Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis.

Apoptosis has been shown to be a significant form of cell loss in many diseases. Detachment of photoreceptors from the retinal pigment epithelium, as seen in various retinal disorders, causes photoreceptor loss and subsequent vision decline. Although caspase-dependent apoptotic pathways are activated after retinal detachment, caspase inhibition by the pan-caspase inhibitor Z-VAD fails to prevent photoreceptor death; thus, we investigated other pathways leading to cell loss.

A novel nonradioactive method to evaluate vascular barrier breakdown and leakage.

Purpose: To identify a novel, sensitive, nonradioactive leakage assay that can be used in the assessment of retinal vascular permeability in rats and mice.

Methods: Breakdown of the vascular barrier was induced by vascular endothelial growth factor (VEGF), lipopolysaccharide (LPS), or diabetes. Biotinylated bovine serum albumin (bBSA) was administered as a tracer.

Development of an efficiently cleaved, bioactive, highly pure FLAG-tagged recombinant human Mullerian Inhibiting Substance.

Mullerian Inhibiting Substance (MIS), a member of the TGF-beta family, causes regression of the Mullerian duct in male embryos, after binding to Mullerian Inhibiting Substance Receptor II (MISRII). It has also been extensively demonstrated that it can inhibit proliferation of various cancer cell lines such as ovarian, prostate, and breast cancer in vitro and in vivo. Hence, the availability of a recombinant, epitope tagged, bioactive MIS is important for the selection of patients for treatment and for probing novel molecular targets for MIS in various tissues.