Energy substrate requirements for survival of rat retinal cells in culture: the importance of glucose and monocarboxylates.
The process of metabolic coupling has been described as a means of providing additional fuel for neurons during periods of intense activity. This process has been suggested to occur in the mammalian retina, but whether retinal neurons can metabolise glial-derived monocarboxylates remains uncertain. The present study therefore sought to define the preferred energy substrates for maintenance of different retinal cells in culture, in order to clarify whether metabolic coupling can potentially occur in this tissue. All cells in rat retinal cultures were detrimentally affected by glucose deprivation. The effect on some neurons, however, could be partially reversed by 5 mm pyruvate or lactate. Furthermore, the glycolytic inhibitor, iodoacetic acid, caused a dose-dependent loss of all retinal cells in culture, whereas the mitochondrial inhibitor, 2,4-dinitrophenol, only led to a decrease in the number of neurons. Finally, inhibition of transporters for glucose or monocarboxylates caused the respective loss of glia or neurons from cultures. These data together demonstrate that, although cells do preferentially metabolise glucose, monocarboxylates such as lactate or pyruvate do play an important role in neuronal maintenance. These data therefore give partial support to the notion that metabolic coupling may occur in the retina.
Wood
John P M
JP
Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK. john.wood@eye.ox.ac.uk
Chidlow
Glyn
G
Graham
Mark
M
Osborne
Neville N
NN
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D007461:Iodoacetates / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism* / Q000494:pharmacology; D019289:Pyruvic Acid / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D012160:Retina / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*
D003470:Culture Media; D007461:Iodoacetates; D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose