Diabetic Retinopathy research studies for holistic treatments

Diabetic retinopathy (DR) is a frequent microvascular complication of diabetes, and one of the most common causes of legal blindness in the world. Epigallocatechin-3-gallate (EGCG) produces an anti-oxidative and anti-inflammatory effect against various human s. In this study, we determined the effect of EGCG on a human retinal endothelial cell (HREC) line. The cell viability was determined by a standard MTT assay, while the cell cycle and apoptosis rate were analyzed by flow cytometry. Inflammatory marker expression was detected by enzyme-linked immunosorbent assay. Treatment of HRECs with EGCG (20 and 40 mM) led to a significant decrease in the apoptosis rate (2.35± 0.56 and 1.24 ± 0.32%). The culture supernatant of cells treated with high glucose concentrations showed significantly higher levels of TNF-? (598.7 ± 89.7 vs 193.2 ± 38.5 pg/mL; P

PURPOSE: Limited mechanistic understanding of diabetic retinopathy (DR) has hindered therapeutic advances. Berberine, an isoquinolone alkaloid, has shown favorable effects on glucose and lipid metabolism in animal and human studies, but effects on DR are unknown. We previously demonstrated intraretinal extravasation and modification of LDL in human diabetes, and toxicity of modified LDL to human retinal Müller cells. We now explore pathogenic effects of modified LDL on Müller cells, and the efficacy of berberine in mitigating this cytotoxicity.
METHODS:
Confluent human Müller cells were exposed to in vitro-modified ‘highly oxidized, glycated (HOG-) LDL versus native-LDL (N-LDL; 200 mg protein/L) for 6 or 24 hours, with/without pretreatment with berberine (5 ?M, 1 hour) and/or the adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitor, Compound C(5 ?M, 1 hour). Using techniques including Western blots, reactive oxygen species (ROS) detection assay, and quantitative real-time PCR, the following outcomes were assessed: cell viability (CCK-8 assay), autophagy (LC3, Beclin-1, ATG-5), apoptosis (cleaved caspase 3, cleaved poly-ADP ribose polymerase), oxidative stress (ROS, nuclear factor erythroid 2-related factor 2, glutathione peroxidase 1, NADPH oxidase 4), angiogenesis (VEGF, pigment epithelium-derived factor), inflammation (inducible nitric oxide synthase, intercellular adhesion molecule 1, IL-6, IL-8, TNF-?), and glial cell activation (glial fibrillary acidic protein).
Results:
Native-LDL had no effect on cultured human Müller cells, but HOG-LDL exhibited marked toxicity, significantly decreasing viability and inducing autophagy, apoptosis, oxidative stress, expression of angiogenic factors, inflammation, and glial cell activation. Berberine attenuated all the effects of HOG-LDL (all P

Diabetic retinopathy is a preventable microvascular diabetic complication and a leading cause of vision loss. Retinal pigment epithelial cell apoptosis is an early event in diabetic retinopathy. Taurine is reportedly beneficial for diabetic retinopathy and is abundant in the fruit of Lycium barbarum (LB). We have investigated the effect of pure taurine and an extract of LB rich in taurine on a model of diabetic retinopathy, the retinal ARPE-19 cell line exposed to high glucose. We demonstrate for the first time that LB extract and the active ligand, taurine, dose dependently enhance cell viability following high glucose treatment in the ARPE-19 retinal epithelial cell line. This cytoprotective effect was associated with the attenuation of high glucose-induced apoptosis, which was shown by characteristic morphological staining and the dose-dependent decrease in the number of apoptotic cells, determined by flow cytometry. Moreover, we have shown that LB extract and taurine dose dependently downregulate caspase-3 protein expression and the enzymatic activity of caspase-3. We conclude that taurine, a major component of LB, and the LB extract, have a cytoprotective effect against glucose exposure in a human retinal epithelial cell line and may provide useful approaches to delaying diabetic retinopathy progression.

The peroxisome proliferator activated receptor-? (PPAR-?) is involved in the pathogenesis of diabetic retinopathy. Diabetic retinopathy is a preventable microvascular diabetic complication that damages human retinal pigment epithelial cells. Taurine is abundant in the fruit of Lycium barbarum (Goji Berry), and is reportedly beneficial for diabetic retinopathy. However, the mechanism of its action is unknown. Hence, we have investigated the mechanism of action of an extract from L. barbarum on a model of diabetic retinopathy, the retinal ARPE-19 cell line, and identified the receptor function of taurine, an active component of L. barbarum (Goji Berry) extract, which is potentially responsible for the protective effect on diabetic retinopathy. We demonstrate for the first time that L. barbarum extract and its taurine component dose-dependently enhance PPAR-? luciferase activity in HEK293 cell line transfected with PPAR-? reporter gene. This activity was significantly decreased by a selective PPAR-? antagonist GW9662. Moreover, L. barbarum extract and taurine dose-dependently enhanced the expression of PPAR-? mRNA and protein. In an inflammation model where ARPE-19 cells were exposed to high glucose L. barbarum extract and taurine down-regulated the mRNA of pro-inflammatory mediators encoding MMP-9, fibronectin and the protein expression of COX-2 and iNOS proteins. The predicted binding mode of taurine in the PPAR-? ligand binding site mimics key electrostatic interactions seen with known PPAR-? agonists. We conclude that PPAR-? activation by L. barbarum extract is associated with its taurine content and may explain at least in part its use in diabetic retinopathy progression.

Background:
Vitamin D status has been hypothesized to protect against development of diabetic retinopathy via its anti-inflammatory and anti-angiogenic properties. Additionally, in vitro and in vivo studies suggest vitamin D favorably influences blood pressure and blood glucose control, strong risk factors for diabetic retinopathy. We examined the association between vitamin D status and prevalent diabetic retinopathy in participants with diabetes from a population-based cohort.
METHODS:
Among participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes at visit 3 (1993-1995), 1339 (906 Caucasians, 433 African Americans) had serum 25-hydroxyvitamin (25[OH]D) concentrations assessed at visit 2 (1989-1992) and nonmydriatic retinal photographs taken at visit 3. Dietary intake of vitamin D was assessed at visit 1 (1987-1989). Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for diabetic retinopathy by categories of season-adjusted 25(OH)D (
Results:
ORs (95 % CIs) for retinopathy, adjusted for race and duration, were 0.77 (0.45-1.32), 0.64 (0.37-1.10), and 0.39 (0.20-0.75), p for trend = 0.001, for participants with 25(OH)D of 30-

Importance: Diabetic retinopathy (DR) is a devastating complication of individuals with type 2 diabetes mellitus. The retina is rich in long-chain?-3 polyunsaturated fatty acids (LC?3PUFAs), which are substrate for oxylipins with anti-inflammatory and antiangiogenic properties. Experimental models support dietary LC?3PUFA protection against DR, but clinical data are lacking. OBJECTIVE:
To determine whether LC?3PUFA intake relates to a decreased incidence of sight-threatening DR in individuals with type 2 diabetes older than 55 years. Design, Setting, and Participants: In late 2015, we conceived a prospective study within the randomized clinical trial Prevención con Dieta Mediterránea (PREDIMED), testing Mediterranean diets supplemented with extra virgin olive oil or nuts vs a control diet for primary cardiovascular prevention. The trial was conducted in primary health care centers in Spain. From 2003 to 2009, 3614 individuals aged 55 to 80 years witha previous diagnosis of type 2 diabetes were recruited. Full data were available for 3482 participants (48% men; mean age 67 years). Exposures: Meeting the dietary LC?3PUFA recommendation of at least 500 mg/d for primary cardiovascular prevention, as assessed by a validated food-frequency questionnaire. Main Outcomes and Measures: The main outcome was incident DR requiring laser photocoagulation, vitrectomy, and/or antiangiogenic therapy confirmed by an external adjudication committee.
Results:
Of the 3482 participants, 48% were men and the mean age was 67 years. A total of 2611 participants (75%) met target LC?3PUFA recommendation. During a median follow-up of 6 years, we documented 69 new events. After adjusting for age, sex, intervention group, and lifestyle and clinical variables, participants meeting the LC?3PUFA recommendation at baseline (?500 mg/d) compared with those not fulfilling this recommendation (Conclusions and Relevance: In middle-aged and older individuals with type 2 diabetes, intake of at least 500 mg/d of dietary LC?3PUFA, easily achievable with 2 weekly servings of oily fish, is associated with a decreased risk of sight-threatening DR. Our results concur with findings from experimental models and the current model of DR pathogenesis. Trial Registration: clinicaltrials.gov Identifier: http://www.controlled-trials.com/ISRCTN35739639.