TNFSF15 Inhibits Blood Retinal Barrier Breakdown Induced by Diabetes.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Blood-Retinal Barrier/*metabolism ; Diabetic Retinopathy/*physiopathology ; Tumor Necrosis Factor Ligand Superfamily Member 15/*metabolism; Aged ; Animals ; Claudin-5/metabolism ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology ; Diabetic Retinopathy/metabolism ; Female ; Genes, Reporter ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Occludin/metabolism ; Rats ; Rats, Wistar ; Retina/metabolism ; Retina/pathology ; Retinal Vessels/metabolism ; Tight Junction Proteins/metabolism ; Tumor Necrosis Factor Ligand Superfamily Member 15/analysis ; Tumor Necrosis Factor Ligand Superfamily Member 15/genetics ; Vascular Endothelial Growth Factor A/analysis

Tumor necrosis factor superfamily 15 (TNFSF15) is an endogenous neovascularization inhibitor and an important negative regulator of vascular homeostasis. This study aimed to explore the potential role of TNFSF15 in diabetic retinopathy. Vitreous TNFSF15 and VEGF levels in proliferative diabetic retinopathy (PDR) patients were detected by ELISA. Retinal expression of TNFSF15 and the content of tight junction proteins (TJPs) in rats were detected by immunohistochemistry and Western blot, respectively. The blood retinal barrier (BRB) permeability was evaluated using Evans Blue (EB) dye. The TNFSF15/VEGF ratio was decreased in the vitreous fluid of patients with PDR relative to the controls, even though the expression levels of TNFSF15 were higher. TNFSF15 was dramatically decreased one month later after diabetes induction (p < 0.001), and then increased three months later and thereafter. TNFSF15 treatment significantly protected the BRB in the diabetic animals. Diabetes decreased TJPs levels in the retina, and these changes were inhibited by TNFSF15 treatment. Moreover, TNFSF15 decreased activation of VEGF both in mRNA and protein levels caused by diabetes. These results indicate that TNFSF15 is an important inhibitor in the progression of DR and suggest that the regulation of TNFSF15 shows promise for the development of diabetic retinopathy treatment strategies.

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Keywords: blood retinal barrier; diabetic retinopathy; tumor necrosis factor superfamily 15; vascular endothelial growth factor; vascular permeability

0 (Claudin-5)
0 (Occludin)
0 (TNFSF15 protein, human)
0 (Tight Junction Proteins)
0 (Tumor Necrosis Factor Ligand Superfamily Member 15)
0 (Vascular Endothelial Growth Factor A)

Date Created: 20160428 Date Completed: 20170216 Latest Revision: 20210109

20231215

PMC4881442

10.3390/ijms17050615

27120595