Mechanisms of neuroprotection by glucose in rat retinal cell cultures subjected to respiratory inhibition

Guoge Han, John P.M. Wood, Glyn Chidlow, Teresa Mammone, Robert J. Casson

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18 Citations (Scopus)


Purpose. Previous experiments have demonstrated that short-term hyperglycemia in rats renders the retina resistant to subsequent metabolic insults. The present study aimed to elucidate putative mechanisms involved in this protective response. 

Methods. Retinal cultures comprising neurons and glia were treated with the mitochondrial complex I inhibitor, rotenone, at a range of concentrations, for up to 24 hours. In some cases, glucose or the alternative energy substrates, pyruvate or lactate, and/or inhibitors of glycolysis or the pentose phosphate pathway (PPP) were also applied. Cell viability was assessed using complementary techniques: immunocytochemistry, immunoblotting, cytotoxicity assay, and TUNEL. Cellular levels of ATP, reactive oxygen species (ROS), and nicotinamide adenine dinucleotide phosphate (NAD[P]H) were also assessed. 

Results. Rotenone caused the preferential loss of neurons from retinal cultures in a concentration-dependent manner; glial cells were also affected, but only at a higher concentrations (10 μM). Cell loss was by apoptosis, and was preceded by a reduction of both cellular ATP and NAD(P)H levels and an increase in the production of ROS. Glucose counteracted the detrimental effects of rotenone. This involved a reduction in ROS levels and an increase in the cellular ATP/NAD(P)H ratio. The protective effect of glucose was partially reversed by either PPP or glycolysis inhibition. 

Conclusions. Glucose rescued cultured rat retinal cells from rotenone-induced toxicity. Glucose acted via both the PPP and the glycolytic pathway, maintaining cellular ATP and NAD(P)H levels and reducing ROS production. These data have implications for treatment of retinal diseases that involve metabolic compromise to neurons.

Original languageEnglish
Pages (from-to)7567-7577
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Issue number12
Publication statusPublished - 22 Oct 2013
Externally publishedYes


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