ArticleBMC ophthalmology2015
Diabetic levels of glucose increase cellular reducing equivalents but reduce survival in three models of 661W photoreceptor-like cell injury.
Article in BMC ophthalmology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Article
- Diabetic photoreceptors: Mechanisms underlying changes in structure and function.Visual neuroscience · 2020Review
- Scanning X-ray microdiffraction of decellularized pericardium tissue at increasing glucose concentration.Journal of biophotonics · 2019Article
- Melatonin receptor heterodimerization in a photoreceptor-like cell line endogenously expressing melatonin receptors.Molecular vision · 2019Article
- High glucose derived endothelial microparticles increase active caspase-3 and reduce microRNA-Let-7a expression in endothelial cells.Biochemical and biophysical research communications · 2017Article
- Melatonin partially protects 661W cells from HMolecular vision · 2017Article
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe effect of excess glucose on retinal cellular health remains controversial, and cellular reducing equivalents, as indicators of cellular energy production, are widely used as substitute indicators of retinal cellular health. These investigations hypothesised that excess energy substrate availability, as occurs in the diabetic retina, increases the susceptibility of retinal neurons to injury in the presence of increased cellular reducing equivalents.
methodsThe response of 661W cells to phototoxicity, oxidative stress induced by H2O2 and apoptosis induction by staurosporine was characterised in the presence of 5mM glucose and B27 defined media without insulin. Cellular insult was produced by phototoxicity, H2O2 and the apoptosis induction agent staurosporine. The effect of physiologically relevant alterations in environmental glucose on cellular reducing equivalents was assessed by MTT dye reduction and NAD(P)H assays, and cell survival was assessed via caspase 3/7 activation and Annexin V/PI flow cytometry.
results661W photoreceptor-like cells underwent dose dependent cell death primarily by apoptosis in response to phototoxic insult, H2O2, and staurosporine by all measures of cellular viability. Exposure of cells to 25mM glucose (diabetic-type conditions) increased cell death in response to all insults as measured by caspase 3/7 activation and Annexin V/PI flow cytometry. Cellular reducing equivalents were nonetheless increased in all models of injury in the presence of excess glucose. The mechanism of this increase was partly due to increased NADPH but not NADH levels in the presence of 25mM glucose.
conclusionsAcute exposure to 25mM glucose decreased the resilience of 661W photoreceptor-like cells to a range of cellular stressors whilst maintaining or increasing cellular reducing equivalents, partly be increasing NADPH levels. This shows that in 661W cells, diabetic levels of glucose decrease cellular resilience to injury. The decoupling of cellular reducing equivalents levels from cell survival has important implications when investigating the mechanisms of neuronal damage in diabetic retinal neuropathy.
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