Diabetic retinopathy is a serious complication of diabetes, marked by retinal vascular damage, inflammation, and angiogenesis. This study's objective was to assess the potential benefits of saroglitazar, a peroxisome proliferator-activated receptor-alpha/gamma (PPAR-α/γ) agonist in diabetic retinopathy. Diabetic retinopathy was induced by streptozotocin in Sprague Dawley rats. The effect of saroglitazar was also assessed in the oxygen-induced retinopathy model in newborn rats and VEGF-induced angiogenesis in the chick chorioallantoic membrane (CAM) assay. Treatment of saroglitazar (1 and 4 mg/kg, oral) for 12 weeks significantly ameliorated retinal vascular leakage and leukostasis in the diabetic rats. Saroglitazar decreased oxidative stress, VEGF receptor signalling, NF-κBp65, and ICAM-1 in the retina of diabetic rats. The beneficial effects of saroglitazar (1 and 4 mg/kg, oral) were also observed on the neovascularization in oxygen-induced retinopathy in newborn rats. Saroglitazar also reduced VEGF-induced angiogenesis in CAM assay. This study reveals that saroglitazar has the potential to prevent the progression of retinopathy in diabetic patients.
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http://dx.doi.org/10.1016/j.ejphar.2021.174032 | DOI Listing |
Front Pharmacol
December 2024
Department of Biosciences, Integral University, Lucknow, India.
Introduction: Diabetic retinopathy is a significant microvascular disorder and the leading cause of vision impairment in working-age individuals. Hyperglycemia triggers retinal damage through mechanisms such as the polyol pathway and the accumulation of advanced glycation end products (AGEs). Inhibiting key enzymes in this pathway, aldose reductase (AR) and sorbitol dehydrogenase (SD), alongside preventing AGE formation, may offer therapeutic strategies for diabetic retinopathy and other vascular complications.
View Article and Find Full Text PDFRetinopathy of prematurity (ROP) and diabetic retinopathy (DR) are ocular disorders in which a loss of retinal vasculature leads to ischemia followed by a compensatory neovascularization response. In mice, this is modeled using oxygen-induced retinopathy (OIR), whereby neonatal animals are transiently housed under hyperoxic conditions that result in central retina vessel regression and subsequent neovascularization. Using endothelial cell (EC)-specific gene deletion, we found that loss of two ETS-family transcription factors, ERG and FLI1, led to regression of OIR-induced neovascular vessels but failed to improve visual function, suggesting that relevant retinal damage occurs prior to and independently of neovascularization.
View Article and Find Full Text PDFOphthalmic Genet
January 2025
Department of Ophthalmology, PSG Institute of Medical Sciences and Research, Coimbatore, India.
Context: The role of genetic factors in the development of diabetic retinopathy is evident from the fact that only 50% of patients with the non-proliferative type of diabetic retinopathy progress to proliferative diabetic retinopathy. Though the K469E polymorphism of the ICAM-1 (Intercellular Adhesion Molecule-1) gene is known to increase the risk of developing Diabetic Retinopathy (DR) among Type 2 diabetic patients, its role in the development of severe DR has not been extensively studied.
Aim: Hence, we aimed to determine the risk due to association of K469E polymorphism of ICAM-1 gene and sight threatening diabetic retinopathy.
J Transl Med
January 2025
Ophthalmic Center, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
Background: The activation of macrophages or microglia in patients' whole body or local eyes play significant roles in diabetic retinopathy (DR). Mitochondrial function regulates the inflammatory polarization of macrophages. Therefore, the common mechanism of mitochondrial related genes (MRGs) and macrophage polarisation related genes (MPRGs) in DR is explored in our study to illustrate the pathophysiology of DR.
View Article and Find Full Text PDFJ Gen Intern Med
January 2025
Western Maine Primary Care, Norway, ME, USA.
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