Metabolic and functional approaches to investigate the effects of cytokines on the physiology of in-vitro and in-vivo models of diabetic retinopathy
type: CreativeWork
description: Diabetic retinopathy (DR) is the leading cause of vision impairment in working age adults worldwide. It is clinically described as hyperglycemia-induced retinal blood vessel damage and is categorized into early non-proliferative and late proliferative stages. Although DR becomes clinically evident only when vascular damage has occurred to the retina, the onset of pathology occurs much earlier than the clinical manifestation. Several studies have reported that metabolic and functional dysregulation in the retina precedes the development of vascular damage in DR. However, current treatment strategies are aimed at treating the late stage sight-threatening vascular problems and do not prevent DR progression. A better understanding of the underlying molecular mechanisms will enable the development of newer therapeutic interventions to modulate these pathways early on and delay the onset of vascular problems. The latest evidence from our lab suggests that in addition to hyperglycemia, retinal inflammation plays an important role in DR development. However, it is still unclear how co-occurrence of hyperglycemia and inflammation alters retinal homeostasis leading to vascular damage. Therefore, the aim of the thesis was to investigate the metabolic and functional effects of pro-inflammatory cytokines on the hyperglycemic retina in an in-vitro and in-vivo DR model. The findings from the in-vitro DR model confirmed that the combined exposure of the retina to high glucose and pro-inflammatory cytokines affected key metabolites including glucose, lactate, ATP and glutamate, and elicited re-distribution of glutamate and glutamine in the retina. These changes suggested that glucose and glutamate metabolic pathways are affected early on in DR. To determine the contribution of glycolysis and glutamate recycling pathways to the metabolic imbalance in DR, the key regulatory enzymes, glyceraldehyde 3-phosphate dehydrogenase and glutamine synthetase were pharmaceutically inhibited, and …
abstract: Diabetic retinopathy (DR) is the leading cause of vision impairment in working age adults worldwide. It is clinically described as hyperglycemia-induced retinal blood vessel damage and is categorized into early non-proliferative and late proliferative stages. Although DR becomes clinically evident only when vascular damage has occurred to the retina, the onset of pathology occurs much earlier than the clinical manifestation. Several studies have reported that metabolic and functional dysregulation in the retina precedes the development of vascular damage in DR. However, current treatment strategies are aimed at treating the late stage sight-threatening vascular problems and do not prevent DR progression. A better understanding of the underlying molecular mechanisms will enable the development of newer therapeutic interventions to modulate these pathways early on and delay the onset of vascular problems. The latest evidence from our lab suggests that in addition to hyperglycemia, retinal inflammation plays an important role in DR development. However, it is still unclear how co-occurrence of hyperglycemia and inflammation alters retinal homeostasis leading to vascular damage. Therefore, the aim of the thesis was to investigate the metabolic and functional effects of pro-inflammatory cytokines on the hyperglycemic retina in an in-vitro and in-vivo DR model. The findings from the in-vitro DR model confirmed that the combined exposure of the retina to high glucose and pro-inflammatory cytokines affected key metabolites including glucose, lactate, ATP and glutamate, and elicited re-distribution of glutamate and glutamine in the retina. These changes suggested that glucose and glutamate metabolic pathways are affected early on in DR. To determine the contribution of glycolysis and glutamate recycling pathways to the metabolic imbalance in DR, the key regulatory enzymes, glyceraldehyde 3-phosphate dehydrogenase and glutamine synthetase were pharmaceutically inhibited, and …
author: Shivashankar, Gaganashree
license: https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm
date published: 2022
date modified: 2026-07-24T01:07:07Z
provider: University of Auckland
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: ResearchSpace@Auckland

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property ID: Handle
value: https://hdl.handle.net/2292/60392