Neuroprotective effects of PPARα in retinopathy of type 1 diabetes.

Diabetic retinopathy (DR) is a common neurovascular complication of type 1 diabetes. Current therapeutics target neovascularization characteristic of end-stage disease, but are associated with significant adverse effects. Targeting early events of DR such as neurodegeneration may lead to safer and more effective approaches to treatment.

Once-Daily Cyclosporine-A-MiDROPS for Treatment of Dry Eye Disease.

Purpose: To determine if a Microemulsion Drug Ocular Penetration System (MiDROPS) formulation of cyclosporine A (CsA) delivers more drug and is more efficacious for treatment of dry eye disease (DED) than the current clinical formulation.

Methods: Tissue distribution of CsA was quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS). To assess tolerability, CsA-MiDROPS (0.

Inhibition of Stat3 by a Small Molecule Inhibitor Slows Vision Loss in a Rat Model of Diabetic Retinopathy.

Purpose: Diabetic retinopathy is a leading cause of vision loss. Previous studies have shown signaling pathways mediated by Stat3 (signal transducer and activator of transcription 3) play a primary role in diabetic retinopathy progression. This study tested CLT-005, a small molecule inhibitor of Stat3, for its dose-dependent therapeutic effects on vision loss in a rat model of diabetic retinopathy.

Molecular pathogenesis of achromatopsia associated with mutations in the cone cyclic nucleotide-gated channel CNGA3 subunit.

Cone photoreceptor cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. Mutations in the cone channel subunits CNGA3 and CNGB3 are linked to achromatopsia and progressive cone dystrophy in humans. Over 50 mutations have been identified in the CNGA3 subunit.

Ocular delivery of compacted DNA-nanoparticles does not elicit toxicity in the mouse retina.

Subretinal delivery of polyethylene glycol-substituted lysine peptide (CK30PEG)-compacted DNA nanoparticles results in efficient gene expression in retinal cells. This work evaluates the ocular safety of compacted DNA nanoparticles. CK30PEG-compacted nanoparticles containing an EGFP expression plasmid were subretinally injected in adult mice (1 microl at 0.

Native cone photoreceptor cyclic nucleotide-gated channel is a heterotetrameric complex comprising both CNGA3 and CNGB3: a study using the cone-dominant retina of Nrl-/- mice.

Cone vision mediated by photoreceptor cyclic nucleotide-gated (CNG) channel activation is essential for central and color vision and visual acuity. Mutations in genes encoding the cone CNG channel subunits, CNGA3 and CNGB3, have been linked to various forms of achromatopsia and progressive cone dystrophy in humans. This study investigates the biochemical components of native cone CNG channels, using the cone-dominant retina in mice deficient in the transcription factor neural retina leucine zipper (Nrl).

Efficient non-viral ocular gene transfer with compacted DNA nanoparticles.

Background: The eye is an excellent candidate for gene therapy as it is immune privileged and much of the disease-causing genetics are well understood. Towards this goal, we evaluated the efficiency of compacted DNA nanoparticles as a system for non-viral gene transfer to ocular tissues. The compacted DNA nanoparticles examined here have been shown to be safe and effective in a human clinical trial, have no theoretical limitation on plasmid size, do not provoke immune responses, and can be highly concentrated.

Retention of function without normal disc morphogenesis occurs in cone but not rod photoreceptors.

It is commonly assumed that photoreceptor (PR) outer segment (OS) morphogenesis is reliant upon the presence of peripherin/rds, hereafter termed Rds. In this study, we demonstrate a differential requirement of Rds during rod and cone OS morphogenesis. In the absence of this PR-specific protein, rods do not form OSs and enter apoptosis, whereas cone PRs develop atypical OSs and are viable.

Absence of functional and structural abnormalities associated with expression of EGFP in the retina.

Purpose: The present study was undertaken to evaluate the effect of uniform EGFP expression on retinal morphology and function.

Methods: Electroretinography (ERG) was used to evaluate the recovery of scotopic a- and b-wave amplitudes after a single 137-cd.sec/m2 flash exposure.

P2Y(2) receptor agonist INS37217 enhances functional recovery after detachment caused by subretinal injection in normal and rds mice.

Purpose: To evaluate the effects of INS37217 on the recovery of retinal function after experimental retinal detachment induced by subretinal injection.

Methods: Subretinal injections of 1 micro L of fluorescent microbeads, saline, or INS37217 (1-200 micro M) were made by the transvitreal method in normal (C57BL/6) mice and in mice heterozygous for the retinal degeneration slow (rds) gene. Control, mock-injected animals underwent corneal puncture without injection.

Loss of bipolar cells resulting from the expression of bcl-2 directed by the IRBP promoter.

We have recently noted marked reductions in the electroretinographic (ERG) b-wave in HIBA transgenic mice expressing bcl-2 under control of the human IRBP promoter. These electrophysiological results are unexpected as this promoter has been shown to specifically target transgene expression to the rod and cone photoreceptors. Here, we have carried out a series of studies to better understand this result.