Tissue Inhibitor of Metalloproteinase-3 Ameliorates Diabetes-Induced Retinal Inflammation

• DOI: 10.3389/fphys.2021.807747
• Publication Date: 2022-01-10T05:28:21Z
• Authors: Ahmed M. Abu El-A...; Ajmal Ahmad; Mohd Imtiaz Nawaz; Mohammad Mairaj S...; Alexandra De Zutter; Lotte Vanbrabant; Priscilla W. Gikandi; Ghislain Opdenakker; Sofie Struyf
• Keywords: 0301 basic medicine; diabetic retinopathy; angiogenesis; blood-retinal barrier; 0303 health sciences; 03 medical and health sciences; inflammation; Physiology; QP1-981; tissue inhibitor of metalloproteinase-3; 3. Good health

Purpose: Endogenous tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) has powerful regulatory effects on inflammation and angiogenesis. In this study, we investigated the role TIMP-3 in regulating diabetic retina. Methods: Vitreous samples from patients with proliferative retinopathy (PDR) non-diabetic were subjected to Western blot analysis. Streptozotocin-treated rats used as a preclinical (DR) model. Blood-retinal barrier (BRB) breakdown was assessed fluorescein isothiocyanate (FITC)-conjugated dextran. Rat retinas, human retinal microvascular endothelial cells (HRMECs) Müller glial studied by analysis ELISA. Adherence monocytes HRMECs vitro angiogenesis assays performed. Results: Tissue vitreous largely glycosylated. Intravitreal injection attenuated diabetes-induced BRB breakdown. This effect associated downregulation upregulation p65 subunit NF-κB, intercellular adhesion molecule-1 (ICAM-1), vascular growth factor (VEGF), whereas phospho-ERK1/2 levels not altered. cell cultures, significantly VEGF induced high-glucose (HG), hypoxia mimetic agent cobalt chloride (CoCl2) TNF-α MCP-1 CoCl2 TNF-α, but HG. HG-induced phospho-ERK1/2, caspase-3 mature form ADAM17, NF-κB proform ADAM17 cells. downregulated TNF-α-induced ICAM-1 VCAM-1 HRMECs. Accordingly, decreased spontaneous TNF-α- VEGF-induced adherence Finally, migration, chemotaxis proliferation Conclusion:In vivo data point anti-inflammatory anti-angiogenic support further studies for its applications treatment DR.