Dataset Information

A Systematic Investigation on Complement Pathway Activation in Diabetic Retinopathy.

ABSTRACT: The complement system plays a crucial role in retinal homeostasis. While the proteomic analysis of ocular tissues in diabetic retinopathy (DR) has shown the deposition of complement proteins, their exact role in the pathogenesis of DR is yet unclear. We performed a detailed investigation of the role of the complement system by evaluating the levels of major complement proteins including C3, C1q, C4b, Complement Factor B (CFB), and Complement Factor H (CFH) and their activated fragments from both the classical and alternative pathways in vitreous humor and serum samples from proliferative DR (PDR) patients and controls. Further, the expressions of complements and several other key pro- and anti-angiogenic genes in the serum and vitreous humor were analyzed in the blood samples of PDR and non-PDR (NPDR) patients along with controls without diabetes. We also assessed the pro-inflammatory cytokines and matrix metalloproteinases in the vitreous humor samples. There was a significant increase in C3 and its activated fragment C3b?' (110 kDa) along with a corresponding upregulation of CFH in the vitreous of PDR patients, which confirmed the increased activation of the alternative complement pathway in PDR. Likewise, a significant upregulation of angiogenic genes and downregulation of anti-angiogenic genes was seen in PDR and NPDR cases. Increased MMP9 activity and upregulation of inflammatory markers IL8 and sPECAM with a downregulation of anti-inflammatory marker IL-10 in PDR vitreous indicated the possible involvement of microglia in DR pathogenesis. Further, a significantly high C3 deposition in the capillary wall along with thickening of basement membranes and co-localization of CFH expression with CD11b+ve activated microglial cells in diabetic retina suggested microglia as a source of CFH in diabetic retina. The increased CFH levels could be a feedback mechanism for arresting excessive complement activation in DR eyes. A gradual increase of CFH and CD11b expression in retina with early to late changes in epiretinal membranes of DR patients indicated a major role for the alternative complement pathway in disease progression.

SUBMITTER: Shahulhameed S

PROVIDER: S-EPMC7026189 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Systematic Investigation on Complement Pathway Activation in Diabetic Retinopathy.

Shahulhameed Shahna S Vishwakarma Sushma S Chhablani Jay J Tyagi Mudit M Pappuru Rajeev R RR Jakati Saumya S Chakrabarti Subhabrata S Kaur Inderjeet I

Frontiers in immunology 20200211

The complement system plays a crucial role in retinal homeostasis. While the proteomic analysis of ocular tissues in diabetic retinopathy (DR) has shown the deposition of complement proteins, their exact role in the pathogenesis of DR is yet unclear. We performed a detailed investigation of the role of the complement system by evaluating the levels of major complement proteins including C3, C1q, C4b, Complement Factor B (CFB), and Complement Factor H (CFH) and their activated fragments from both ...[more]

PMID: 32117292

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Project description:AimTo investigate reasons for delayed presentation in patients with proliferative diabetic retinopathy (PDR).MethodsA questionnaire was designed to investigate consecutive PDR patients with delayed presentation who visited our center between January 2021 and December 2021. The questionnaire was divided into four sections: knowledge regarding diabetic retinopathy (DR), attitude toward DR treatment, difficulties adhering to follow-up plans, and medical care. The systemic disease status and severity of DR were recorded. Logistic analysis was undertaken to investigate DR treatment refusal and delay factors.ResultsA total of 157 patients were included in this study, with an average age of 50.0 ± 11.6 years. The median glycated hemoglobin level (HbA1c) was 7.8% (IQR 2.5%). Among the 157 eyes, most required vitrectomy intervention (144, 91.7%); 17 developed neovascular glaucoma (NVG), while only 13 required additional photocoagulation. Among the 36 patients with undiagnosed DM, the reason for delayed DR presentation was a lack of awareness of DM status among these patients (36 cases, 100.0%). Most of the patients with a known history of DM exhibited inadequate DR knowledge (29, 24.0%), believed their good visual acuity did not require DR screening (98, 81.0%), and had poorly controlled diabetes (113, 93.3%). Factors related to refusing DR treatment were patients with an inability to receive regular diabetes treatment in internal medicine clinics (OR 6.78, 95% CI 1.73-26.59, p = 0.006), patients who could not tolerate discomfort during ophthalmic examination and treatment (OR 15.15, 95% CI 2.70-83.33, p<0.001), and patients who did not have any retinal abnormalities detected and were not informed about the need for regular screening (OR 2.05, 95% CI 1.36-3.09, p<0.001).ConclusionsThis study investigated the factors contributing to delayed presentation among patients with PDR. Many individuals in the delayed population were found to have undiagnosed DM. Among patients already aware of their DM status, reasons for delay included insufficient knowledge about DR, negative attitudes toward screening and treatment, and difficulties seeking medical care in real-life situations. Furthermore, there needed to be more improvements in the detection, treatment, and follow-up of DR by internal medicine practitioners and ophthalmologists.

Dataset Information

A Systematic Investigation on Complement Pathway Activation in Diabetic Retinopathy.

Publications

A Systematic Investigation on Complement Pathway Activation in Diabetic Retinopathy.

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