Hydrogen Sulfide Is a Novel Protector of the Retinal Glycocalyx and Endothelial Permeability Barrier

• Published in: Frontiers in cell and developmental biology 2021-09, Vol.9, p.724905-724905
• Main Authors: Allen, Claire L, Wolanska, Katarzyna, Malhi, Naseeb K, Benest, Andrew V, Wood, Mark E, Amoaku, Winfried, Torregrossa, Roberta, Whiteman, Matthew, Bates, David O, Whatmore, Jacqueline L
• Format: Article
• Language: English
• Subjects: Cell and Developmental Biology; diabetes; glycocalyx; hydrogen sulfide; inflammation; mitochondria; retinal permeability
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2021.724905

Significantly reduced levels of the anti-inflammatory gaseous transmitter hydrogen sulfide (H S) are observed in diabetic patients and correlate with microvascular dysfunction. H S may protect the microvasculature by preventing loss of the endothelial glycocalyx. We tested the hypothesis that H S could prevent or treat retinal microvascular endothelial dysfunction in diabetes. Bovine retinal endothelial cells (BRECs) were exposed to normal (NG, 5.5 mmol/L) or high glucose (HG, 25 mmol/L) ± the slow-release H S donor NaGYY4137 . Glycocalyx coverage (stained with WGA-FITC) and calcein-labeled monocyte adherence were measured. , fundus fluorescein angiography (FFA) was performed in normal and streptozotocin-induced (STZ) diabetic rats. Animals received intraocular injection of NaGYY4137 (1 μM) or the mitochondrial-targeted H S donor AP39 (100 nM) simultaneously with STZ (prevention) or on day 6 after STZ (treatment), and the ratio of interstitial to vascular fluorescence was used to estimate apparent permeability. NaGYY4137 prevented HG-induced loss of BREC glycocalyx, increased monocyte binding to BRECs ( ≤ 0.001), and increased overall glycocalyx coverage ( ≤ 0.001). In rats, the STZ-induced increase in apparent retinal vascular permeability ( ≤ 0.01) was significantly prevented by pre-treatment with NaGYY4137 and AP39 ( < 0.05) and stabilized by their post-STZ administration. NaGYY4137 also reduced the number of acellular capillaries (collagen IV + /IB4-) in the diabetic retina in both groups ( ≤ 0.05). We conclude that NaGYY4137 and AP39 protected the retinal glycocalyx and endothelial permeability barrier from diabetes-associated loss of integrity and reduced the progression of diabetic retinopathy (DR). Hydrogen sulfide donors that target the glycocalyx may therefore be a therapeutic candidate for DR.