151. Glucosamine protects against neuronal but not vascular damage in experimental diabetic retinopathy
- Author
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Di Zhao, Thomas Wieland, Yuxi Feng, Katharina Murillo, Gregor Jainta, Martina Schmidt, Loïc Dongmo Teuma, Rachana Eshwaran, Hans-Peter Hammes, Gernot Poschet, M Kolibabka, Molecular Pharmacology, and Groningen Research Institute for Asthma and COPD (GRIAC)
- Subjects
Male ,medicine.medical_specialty ,Neuronal ,Endothelial cells ,Osteoarthritis ,Vascular damage ,Protective Agents ,Retina ,chemistry.chemical_compound ,Mice ,In vivo ,Glucosamine ,Internal medicine ,Diabetes mellitus ,medicine ,Animals ,Humans ,Molecular Biology ,Cells, Cultured ,Müller cells ,Neurons ,Diabetic Retinopathy ,business.industry ,Cell Biology ,Diabetic retinopathy ,medicine.disease ,RC31-1245 ,In vitro ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Original Article ,Pericyte ,business - Abstract
Objective Glucosamine, an intermetabolite of the hexosamine biosynthesis pathway (HBP), is a widely used nutritional supplement in osteoarthritis patients, a subset of whom also suffer from diabetes. HBP is activated in diabetic retinopathy (DR). The aim of this study is to investigate the yet unclear effects of glucosamine on DR. Methods In this study, we tested the effect of glucosamine on vascular and neuronal pathology in a mouse model of streptozotocin-induced DR in vivo and on cultured endothelial and Müller cells to elucidate the underlying mechanisms of action in vitro. Results Glucosamine did not alter the blood glucose or HbA1c levels in the animals, but induced body weight gain in the non-diabetic animals. Interestingly, the impaired neuronal function in diabetic animals could be prevented by glucosamine treatment. Correspondingly, the activation of Müller cells was prevented in the retina as well as in cell culture. Conversely, glucosamine administration in the normal retina damaged the retinal vasculature by increasing pericyte loss and acellular capillary formation, likely by interfering with endothelial survival signals as seen in vitro in cultured endothelial cells. Nevertheless, under diabetic conditions, no further increase in the detrimental effects were observed. Conclusions In conclusion, the effects of glucosamine supplementation in the retina appear to be a double-edged sword: neuronal protection in the diabetic retina and vascular damage in the normal retina. Thus, glucosamine supplementation in osteoarthritis patients with or without diabetes should be taken with care., Highlights • The hexosamine biosynthesis pathway (HBP) is activated in diabetic retinopathy (DR), which manifests as vascular and neuronal damage in the retina. • Glucosamine, metabolized in the HBP, is a widely used oral supplement for osteoarthritis treatment. • Glucosamine supplementation improved neuronal function in retinas of mice with experimental DR, but induced vascular damage in normal retinas. • Müller cell activation and endothelial survival signals in the retina were affected by glucosamine. • Patients with or without diabetes should take caution with glucosamine supplementation.
- Published
- 2021