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Glaucoma is one of the most common sight-threatening eye disorders and one of the main causes of irreversible blindness worldwide. The current therapies focusing on reducing intraocular pressure (IOP) are often insufficient to prevent the progression of the disease, so the therapeutic management of glaucoma remains a challenge. The aim of this study was to evaluate the neuroprotective, IOP-lowering independent effects of a nutritional supplement containing forskolin, homotaurine, spearmint extract and vitamins of the B group in a model of acute glaucoma developed in mice. Glaucoma was induced in adult wild-type C57BL/6J mice by transient elevation of IOP. The dietary supplement, branded as Gangliomix® (125 mg/kg/day), was administered by oral gavage for 17 days and ocular hypertension was induced on the 10th day of treatment. A histological analysis of the retinas was performed and RGC survival was evaluated with fluorogold labeling and Brn3a immunostaining on wholemount and retinal sections. Expression of alpha-spectrin, caspase-3, PARP-1 and GFAP was studied with western blotting or immunofluorescence. A significant increase in RGC survival was reported in the retina of mice treated with the dietary supplement as compared to vehicle-treated animals. The observed neuroprotection was associated with a calpain activity decrease, reduction in caspase-3 and PARP-1 activation, and prevention of GFAP upregulation. These effects were independent from the hypotensive effects of the supplement. Altogether, our data suggest that the dietary supplementation with forskolin, homotaurine, spearmint extract and vitamins of the B group supports RGC survival and may offer beneficial effects in glaucoma patients in combination with the currently used IOP-lowering therapy.

Autophagy is the major catabolic pathway involved in removing and recycling damaged macromolecules and organelles and several evidences suggest that dysfunctions of this pathway contribute to the onset and progression of central and peripheral neurodegenerative diseases. Diabetic retinopathy (DR) is a serious complication of diabetes mellitus representing the main preventable cause of acquired blindness worldwide. DR has traditionally been considered as a microvascular disease, however this concept has evolved and neurodegeneration and neuroinflammation have emerged as important determinants in the pathogenesis and evolution of the retinal pathology. Here we review the role of autophagy in experimental models of DR and explore the potential of this pathway as a target for alternative therapeutic approaches.

IntroductionGlucosamine, the intermediate metabolite of the hexosamine biosynthesis pathway (HBP), is widely used as a supplementary drug in patients with osteoarthritis. However, its consequences in such patients concomitantly suffering from diabetic nephropathy is unknown.MethodsThe aim of the study was to investigate the effect of exogenous administration of glucosamine in the diabetic kidney. A mouse model of streptozotocin-induced diabetic nephropathy in vivo and cultured endothelial cells in vitro were used in the study. The mice were treated with glucosamine for 6 months. Renal function was evaluated by metabolic cage, and histology of the kidney was estimated by periodic acid-schiff (PAS) staining. The expression of related genes was assessed by real-time PCR, immunofluorescence staining, immunoblotting and ELISA.ResultsThere was no significant difference in urinary albumin secretion, relative kidney weight, or creatinine clearance between the groups treated with glucosamine and controls. Assessment of the kidney demonstrated reduction in mesangial expansion and fibronectin expression in the diabetic glomeruli treated with glucosamine. Glucosamine treatment significantly decreased α-smooth muscle actin (α-SMA) protein expression in both diabetic and control kidneys, whereas the expression of other fibrosis-related genes and inflammatory factors was unaltered. Moreover, α-SMA colocalized with the endothelial marker CD31 in the diabetic and control kidneys, and glucosamine reduced α-SMA+ ECs in the diabetic glomeruli. In addition, glucosamine suppressed α-SMA expression in endothelial cells treated with or without high glucose.DiscussionIn summary, this is the first report to show that glucosamine reduces mesangial expansion and inhibits endothelial-mesenchymal transition in diabetic nephropathy. The underlying mechanisms need to be further investigated.