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Frontiers in Understanding the Pathological Mechanism of Diabetic Retinopathy.

ABSTRACT: The retina is a light-sensitive membrane responsible for optical signal reception and concatenation with the optic nerve. Retinal damage causes blurred vision or visual dysfunction. Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM) that is induced by the interaction of multiple factors and mechanisms. Hyperglycemia and hypertension are potential risk factors for DR. With the growing number of DM patients, the incidence of DR increases if DM is untreated. Epidemiological data show that DR is a leading cause of blindness in working-aged adults. Regular ophthalmological check-ups, laser treatment, and interdisciplinary consultation for reducing visual atrophy can help prevent and treat DR. Although the pathogenesis of DR is complex, and the exact pathological mechanism of DR needs to be further elucidated to promote new drug research and development against DR. The entire pathological process of DR involves increased oxidative stress (microvascular dysfunction, mitochondrial dysfunction) and chronic inflammation (inflammatory infiltration, cell necrosis) and impairment of the renin-angiotensin system (microcirculation dysregulation). This review aims to summarize the pathological mechanisms underlying the development of DR to improve clinical diagnosis and effective treatment of DR.

SUBMITTER: Zhan L

PROVIDER: S-EPMC10274216 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Frontiers in Understanding the Pathological Mechanism of Diabetic Retinopathy.

Zhan Lei L

Medical science monitor : international medical journal of experimental and clinical research 20230612

The retina is a light-sensitive membrane responsible for optical signal reception and concatenation with the optic nerve. Retinal damage causes blurred vision or visual dysfunction. Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM) that is induced by the interaction of multiple factors and mechanisms. Hyperglycemia and hypertension are potential risk factors for DR. With the growing number of DM patients, the incidence of DR increases if DM is untreated. ...[more]

PMID: 37307243

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Project description:To investigate the effect of scutellarin (SCU) in diabetic retinopathy (DR) and explore the associated molecular network mechanism. The animal model of DR was established from diabetic mellitus (DM) rats by intraperitoneally injected streptozotocin (STZ) at dosage 55 mg/kg. Meanwhile, SCU was intraperitoneally administrated to protect retina from cell pyroptosis induced by DM, and cell pyroptosis was detected by using HE, Nissl staining, and immunofluorescence recognition. Moreover, the hub gene involving in pyroptosis in DR was screened by bioinformatics and network pharmacology, designated as Venny intersection screen, GO and KEGG analysis, PPI protein interaction, and molecular docking. Lastly, the expressional change of hub genes were validated with experimental detection. Cell pyroptosis of the DR, specifically in retina ganglion cells (RGC), was induced in DM rats; SCU administration results in significant inhibition in the cell pyroptosis in DR. Mechanically, 4084 genes related to DR were screened from GeneCards and OMIM databases, and 120 SCU therapeutic targets were obtained, by using GeneCards, TCMSP with Swiss Target Prediction databases. Moreover, 357 targets related to pyroptosis were found using GenenCards database, and Drug, disease and phenotypic targets were analyzed online using the Draw Venn Diagram website, and 12 cross targets were obtained. Through GO function and KEGG pathway enrichment analysis, 659 BP related items, 7 CC related items, 30 MF related items, and 70 signal pathways were screened out; Of these, eleven proteins screened from cross-target PPI network were subsequently docked with the SCU, and their expressions including caspase-1, IL-1β, IL-18, GSDMD and NLRP3 in RGC indicated by immunofluorescence, and the mRNA expression for caspase-1 in DR indicated by quantitative PCR, were successfully validated. SCU can effectively protect RGC pyroptosis in DR, and underlying mechanisms are involved in the inhibition of caspase-1, GSDMD, NLRP3, IL-1β and IL-18. Our findings therefore provide crucial evidence to support the clinic practice of SCU for the treatment of DR, and explained the underlying molecular network mechanism.

Project description:PurposeTo identify the protein profiles in vitreous associated with retinal fibrosis, angiogenesis, and neurite formation in epiretinal fibrovascular membranes (FVMs) in patients with proliferative diabetic retinopathy (PDR).MethodsVitreous samples of 5 non-diabetic control patients with vitreous debris and 7 patients with PDR membranes were screened for 507 preselected proteins using the semi-quantitative RayBio® L-series 507 antibody array. From this array, 60 proteins were selected for a custom quantitative antibody array (Raybiotech, Human Quantibody® array), analyzing 7 control patients, 8 PDR patients with FVMs, and 5 PDR patients without FVMs. Additionally, mRNA levels of proteins of interest were measured in 10 PDR membranes and 11 idiopathic membranes and in retinal tissues and cells to identify possible sources of protein production.ResultsOf the 507 proteins screened, 21 were found to be significantly elevated in PDR patients, including neurogenic and angiogenic factors such as neuregulin 1 (NRG1), nerve growth factor receptor (NGFR), placental growth factor (PlGF) and platelet derived growth factor (PDGF). Angiopoietin-2 (Ang2) concentrations were strongly correlated to the degree of fibrosis and the presence of FVMs in patients with PDR. Protein correlation analysis showed PDGF to be extensively co-regulated with other proteins, including thrombospondin-1 and Ang2. mRNA levels of glial-derived and brain/derived neurotrophic factor (GDNF and BDNF) were elevated in PDR membranes. These results were validated in a second study of 52 vitreous samples of 32 PDR patients and 20 control patients.ConclusionsThis exploratory study reveals protein networks that potentially contribute to neurite outgrowth, angiogenesis and fibrosis in the formation of fibrovascular membranes in PDR. We identified a possible role of Ang2 in fibrosis and the formation of FVMs, and of the neurotrophic factors NRG1, PDGF and GDNF in neurite growth that occurs in all FVMs in PDR.

Dataset Information

Frontiers in Understanding the Pathological Mechanism of Diabetic Retinopathy.

Publications

Frontiers in Understanding the Pathological Mechanism of Diabetic Retinopathy.

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