Tissue Inhibitor of Metalloproteinase-3 Ameliorates Diabetes-Induced Retinal Inflammation
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
DOI:
10.3389/fphys.2021.807747
Publication Date:
2022-01-10T05:28:21Z
AUTHORS (9)
ABSTRACT
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.
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