Celastrol inhibits laser-induced choroidal neovascularization by decreasing VEGF induced proliferation and migration.

Aim: To evaluate celastrol's effect on choroidal neovascularization (CNV).

Methods: In this study, neovascular formation (tube formation and aortic ring culture) and (laser induced neovascular in mice) was treated with celastrol to evaluate this natural compound's impact on CNV. Western blot was applied to explore the possible mechanism for it.

Anti-viral activity of lysates against herpes simplex virus type-I infection: an and study.

Aim: To investigate the effect of lysates (SALs) on herpes simplex virus type-I (HSV1) infection in human corneal epithelial (HCE) cells and in a mouse model of HSV1 keratitis.

Methods: HCE, Vero, HeLa, and BV2 cells were infected with HSV1 [HSV1 f strain, HSV1f; HSV-1-H129 with green fluorescent protein (GFP) knock-in, HSV1g]. Pre- or post-infection, SAL at various concentrations was added to the culture medium for 24h.

Association between dietary antioxidants and risk for diabetic retinopathy in a Chinese population.

Background: Diabetic retinopathy (DR) is related to oxidative stress and insufficient intake of dietary antioxidants may be associated with the onset and progression of DR. This study aimed to detect the association between main dietary antioxidants intake and the risk for DR.

Methods: This is a cross-sectional study of a Chinese urban population.

Celastrol Protects RPE Cells from Oxidative Stress-Induced Cell Death via Activation of Nrf2 Signaling Pathway.

Purpose: Oxidative stress to retinal pigment epithelial (RPE) cells and inflammation are closely related to the pathogenesis of age-related macular degeneration (AMD). Celastrol is a natural compound isolated from the root of Tripterygium wilfordii. Celastrol has been shown to have potent anti-inflammatory and anti-tumor effects in multiple disease models.

Celastrol Ameliorates Inflammation in Human Retinal Pigment Epithelial Cells by Suppressing NF-κB Signaling.

Purpose: Celastrol is a triterpenoid quinine methide that exerts important biological effects on a variety of disease models. In this study, we aim to assess the ability of celastrol to inhibit lipopolysaccharide (LPS)-induced inflammation in retinal pigment epithelial (RPE) cells.

Methods: Primary cultures of human RPE (HRPE) cells and ARPE-19 cell lines were treated with celastrol alone or in combination with LPS.

Effect of an MG132-Sustained Drug Delivery Capsular Ring on the Inhibition of Posterior Capsule Opacification in a Rabbit Model.

Purpose: To design an MG132-sustained drug delivery capsular ring (SDDCR) and investigate its effect on the inhibition of posterior capsule opacification (PCO) in a rabbit model.

Methods: The SDDCRs were prepared by forming a slice of film made by the mixture of poly lactic-co-glycolic acid (PLGA) and MG132 on the surface of capsular tension rings (CTRs). The drug-loading capacity, entrapment efficiency, and in vitro release of the drug-containing film were detected.

Fasudil inhibits LPS-induced migration of retinal microglial cells via regulating p38-MAPK signaling pathway.

Purpose: To investigate the effect and possible molecular mechanisms of fasudil on retinal microglial (RMG) cell migration.

Methods: Primary cultured RMG cells were incubated with lipopolysaccharide (LPS), fasudil, and/or SB203580 (a p38 inhibitor). RMG cell motility was determined with the scratch wound assay and the Transwell migration assay.

Lens regeneration using endogenous stem cells with gain of visual function.

The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens.

Lithium ions attenuate serum-deprivation-induced apoptosis in PC12 cells through regulation of the Akt/FoxO1 signaling pathways.

Rationale: Lithium is currently used in the treatment of mental illness. We have previously reported that lithium stimulated the protein kinase B/Forkhead box O1 (Akt/FoxO1) pathway in rats. However, little information is available regarding its neuroprotective role of this pathway and underlying mechanisms.

Unfolded-protein response-associated stabilization of p27(Cdkn1b) interferes with lens fiber cell denucleation, leading to cataract.

Failure of lens fiber cell denucleation (LFCD) is associated with congenital cataracts, but the pathobiology awaits elucidation. Recent work has suggested that mechanisms that direct the unidirectional process of LFCD are analogous to the cyclic processes associated with mitosis. We found that lens-specific mutations that elicit an unfolded-protein response (UPR) in vivo accumulate p27(Cdkn1b), show cyclin-dependent kinase (Cdk)-1 inhibition, retain their LFC nuclei, and are cataractous.

Altered ubiquitin causes perturbed calcium homeostasis, hyperactivation of calpain, dysregulated differentiation, and cataract.

Although the ocular lens shares many features with other tissues, it is unique in that it retains its cells throughout life, making it ideal for studies of differentiation/development. Precipitation of proteins results in lens opacification, or cataract, the major blinding disease. Lysines on ubiquitin (Ub) determine fates of Ub-protein substrates.

Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly.

Lens epithelial cells and early lens fiber cells contain the typical complement of intracellular organelles. However, as lens fiber cells mature they must destroy their organelles, including nuclei, in a process that has remained enigmatic for over a century, but which is crucial for the formation of the organelle-free zone in the center of the lens that assures clarity and function to transmit light. Nuclear degradation in lens fiber cells requires the nuclease DNase IIβ (DLAD) but the mechanism by which DLAD gains access to nuclear DNA remains unknown.

High glucose activates ChREBP-mediated HIF-1α and VEGF expression in human RPE cells under normoxia.

Objective: Because retina-damaging angiogenesis is controlled by vascular endothelial growth factor (VEGF) and people with higher glucose intakes are more susceptible to retinal complications that may be due to increased VEGF, it is crucial to elucidate relations between glucose exposure and VEGF expression. We aimed to determine if a carbohydrate response element binding protein (ChREBP) plays a role in the transcriptional up-regulation of hypoxia-inducible factor-1α (HIF-1α) and the downstream VEGF expression in retinal pigment epithelial (RPE) cells exposed to high glucose under normoxic conditions.

Methods: ARPE19 cells were exposed to 5.

Impairment of the ubiquitin-proteasome pathway in RPE alters the expression of inflammation related genes.

The ubiquitin-proteasome pathway (UPP) plays an important role in regulating gene expression. Retinal pigment epithelial cells (RPE) are a major source of ocular inflammatory cytokines. In this work we determined the relationship between impairment of the UPP and expression of inflammation-related factors.

Newborn mouse lens proteome and its alteration by lysine 6 mutant ubiquitin.

Ubiquitin is a tag that often initiates degradation of proteins by the proteasome in the ubiquitin proteasome system. Targeted expression of K6W mutant ubiquitin (K6W-Ub) in the lens results in defects in lens development and cataract formation, suggesting critical functions for ubiquitin in lens. To study the developmental processes that require intact ubiquitin, we executed the most extensive characterization of the lens proteome to date.

Synchrotron infrared imaging of advanced glycation endproducts (AGEs) in cardiac tissue from mice fed high glycemic diets.

Recent research findings correlate an increased risk for dieases such as diabetes, macular degeneration and cardiovascular disease (CVD) with diets that rapidly raise the blood sugar levels; these diets are known as high glycemic index (GI) diets which include white breads, sodas and sweet deserts. Lower glycemia diets are usually rich in fruits, non-starchy vegetables and whole grain products. The goal of our study was to compare and contrast the effects of a low vs.

Enhancement of ubiquitin conjugation activity reduces intracellular aggregation of V76D mutant γD-crystallin.

Purpose: The ubiquitin-proteasome pathway (UPP) is an important protein quality control mechanism for selective degradation of abnormal proteins. The objective of this study was to test the hypothesis that enhancement of the UPP capacity could attenuate the accumulation and aggregation of misfolded proteins using V76D-γD-crystallin as a model substrate.

Methods: Wild type (wt) and V76D mutant γD-crystallin were fused to red fluorescence protein (RFP) and expressed in human lens epithelial cells.

Lutein and zeaxanthin supplementation reduces photooxidative damage and modulates the expression of inflammation-related genes in retinal pigment epithelial cells.

Oxidative damage and inflammation are related to the pathogenesis of age-related macular degeneration (AMD). Epidemiologic studies suggest that insufficient dietary lutein and zeaxanthin intake or lower serum zeaxanthin levels are associated with increased risk for AMD. The objective of this work is to test the protective effects of lutein and zeaxanthin against photooxidative damage to retinal pigment epithelial cells (RPE) and oxidation-induced changes in expression of inflammation-related genes.

Role of the ubiquitin-proteasome in protein quality control and signaling: implication in the pathogenesis of eye diseases.

The ubiquitin-proteasome pathway (UPP) plays important roles in many cellular functions, such as protein quality control, cell cycle control, and signal transduction. The selective degradation of aberrant proteins by the UPP is essential for the timely removal of potential cytotoxic damaged or otherwise abnormal proteins. Conversely, accumulation of the cytotoxic abnormal proteins in eye tissues is etiologically associated with many age-related eye diseases such as retina degeneration, cataract, and certain types of glaucoma.

Roles for the ubiquitin-proteasome pathway in protein quality control and signaling in the retina: implications in the pathogenesis of age-related macular degeneration.

The accumulation of damaged or postsynthetically modified proteins and dysregulation of inflammatory responses and angiogenesis in the retina/RPE are thought be etiologically related to formation of drusen and choroidal neovascularization (CNV), hallmarks of age-related macular degeneration (AMD). The ubiquitin-proteasome pathway (UPP) plays crucial roles in protein quality control, cell cycle control and signal transduction. Selective degradation of aberrant proteins by the UPP is essential for timely removal of potentially cytotoxic damaged or otherwise abnormal proteins.

Oligomerization with wt αA- and αB-crystallins reduces proteasome-mediated degradation of C-terminally truncated αA-crystallin.

Purpose: We previously demonstrated that the ubiquitin-proteasome pathway (UPP) is a general protein quality control system that selectively degrades damaged or abnormal lens proteins, including C-terminally truncated αA-crystallin. The objective of this work was to determine the effects of wt αA- and αB-crystallins on the degradation of C-terminally truncated αA-crystallin (αA(1-162)) and vice versa.

Methods: Recombinant wt αA, αB, and αA(1-162) were expressed in Escherichia coli and purified to homogeneity by chromatography.

Measurement of macular pigment optical density in a healthy Chinese population sample.

Purpose: Macular pigment may protect against age-related macular degeneration (AMD) by its capacity to absorb blue light and scavenge free radicals. Current information on human macular pigment density has been largely from studies on Caucasian populations. The purpose of this study was to assess macular pigment density and its determinant factors in a Chinese population sample.