title: Investigation of the potential role of glucosamine in experimental diabetic retinopathy
creator: Eshwaran, Rachana
subject: ddc-570
subject: 570 Life sciences
description: The hexosamine biosynthesis pathway (HBP), an offshoot of glycolysis, functions as a nutrient sensing pathway, and incorporates elements of amino acid, fatty acid, glucose, and nucleotide metabolisms. The HBP is implicated in post-translational protein modification via O-GlcNAc cycling, and plays a role in the initiation and progression of diabetic retinopathy.  Glucosamine, an intermetabolite in the HBP, is a hexose sugar that is found naturally occurring in bones and crustacean shells. It is currently widely prescribed as an oral supplement in the treatment of osteoarthritis to promote cartilage renewal and to restore normal joint function. Due to its antioxidative and anti-inflammatory properties, and its role in the HBP, the aim of this study was to investigate the role of glucosamine in an experimental model of diabetic retinopathy, and to uncover the underlying mechanism of action using cultured cell models. The general metabolic parameters including blood glucose, HbA1c, the consumption of food and  water, and the subsequent excretion of urine and feces were unaffected by glucosamine supplementation in the diet. Despite this, the non-diabetic animals treated with glucosamine exhibited a body weight gain compared to the controls. Examination of the neuroretinal function in vivo via electroretinogram (ERG) showed that supplementation of glucosamine reduced the P1-wave amplitude elevated in diabetic animals,  suggesting an improvement in neuroretinal function possibly via modulation of Müller cells. Moreover, cultured Müller cells treated with glucosamine demonstrated a decrease in GFAP expression, suggesting an amelioration in Müller cell function that correlates with the in vivo ERG  results. Additionally, reduction in VEGF expression in the Müller cells upon glucosamine treatment was detected, indicating a possible impact of glucosamine on retinal vasculature. However, glucosamine supplementation induced vascular damage in the retina, which is also a prominent characteristic in diabetic retinopathy. Unexpectedly, similar to the diabetic animals, glucosamine-treated retinas showed increased pericyte loss and acellular capillary numbers in the non-diabetic and diabetic retinas. The assessment of endothelial signaling showed a dose-dependent decrease in Ang2 and VEGFR2 protein levels upon glucosamine treatment in both normal and high glucose conditions, suggesting that glucosamine may cause vascular damage by interfering with endothelial survival signals.  In conclusion, glucosamine can have multi-faceted effects, and any supplementation, especially in osteoarthritis patients suffering concomitantly with diabetes, should be taken with care.
date: 2022
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/32408/1/Thesis_Rachana%20Eshwaran.pdf
identifier: DOI:10.11588/heidok.00032408
identifier: urn:nbn:de:bsz:16-heidok-324085
identifier:   Eshwaran, Rachana  (2022) Investigation of the potential role of glucosamine in experimental diabetic retinopathy.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/32408/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng