W167 - Platelet-mediated Neutrophil Extracellular Traps (NETs) Aggravate the Development and Progression of Diabetic Retinopathy

Wednesday, June 25, 2025

7:30am - 7:30pm East Coast USA Time

BN

Bishamber Nath, M. Pharm

PhD Scholar
National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Guwahati, Assam, 781101, India
guwahati, Assam, India
SM

Suraj B. Mungase, M. Pharm.

National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Guwahati, Assam, 781101, India
PB

Priyank Bhola

Sri Sankaradeva Nethralaya, Guwahati–781028, Assam, India.
MB

Manabjyoti Barman

Sri Sankaradeva Nethralaya, Guwahati–781028, Assam, India.
RD

Rupam Das

Down Town Hospital, Guwahati, Assam, 781006, India
RA

Ramu Adela, M Pharm, PhD

National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Guwahati, Assam, 781101, India

Abstract Text:

Background: Activated platelets and neutrophils are associated with the development and progression of type 2 diabetes mellitus (T2DM). However, platelet-neutrophil interactions in the pathogenesis of diabetic retinopathy (DR) are less explored. Therefore, we aimed to assess the role of platelet-mediated neutrophils extracellular traps (NETs) in the pathogenesis of DR.
Methodology: Platelet activation, platelet-neutrophil aggregates (PNA), NETs, and circulatory level of inflammatory cytokines/chemokines were measured in healthy control (HC), T2DM, non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) subjects. Further, PNA, platelet-induced NETs, and NETs-induced Angiogenesis were assessed by ex-vivo and in-vitro studies. LC-MS/MS based SWATH analysis was performed to explore the molecular mechanism of platelet-induced NETs in DR.

Results: Platelet activation, PNA, and NETs were significantly increased in T2DM, NPDR, and PDR compared to HC subjects. A positive correlation was found between platelet activation, PNA, and NETs. Furthermore, NETs were positively correlated with angiogenic and inflammatory markers (angiopoietin-2, ICAM-1, and IL-18). DR-platelets induced higher PNA and NETs compared to T2DM and HC-platelets. NETs induced by DR-Platelet induce angiogenesis in the RF/6A cell spheroids as compared to HC and T2DM platelet-induced NETs Proteomics analysis revealed that platelet-related proteins (CXCL7, WDR-1, vWF) were differentially expressed in DR and T2DM platelet-induced NETs compared to HC platelet-induced NETs.

Conclusion: Our findings revealed that platelets get activated by a prolonged hyperglycemic environment, platelets further release inflammatory cytokines/chemokines and aggregate with neutrophils and prime neutrophils towards NETs formation. NETs further promote angiogenesis and contribute towards the progression of DR.
Keywords: Diabetic retinopathy, Platelet, Neutrophil, NETs