Abstract
Purpose :
The retina has the greatest metabolic demand in the body and ageing and disease impact on its central region, which has a distinct architecture and very high cell density. Here we ask how the primate retina and RPE derive energy for cellular function.
Methods :
We use eyes from 10 cynomolgous long-tailed monkeys (Macaca fascicularis) which were donated at death and were between 4 and 14 years old. Mitochondrial function and glycolysis were analysed using Western blot and immunohistochemistry of different subunits of cytochrome C oxidase and lactate and pyruvate dehydrogenases.
Results :
Mitochondrial function was assessed by analysis of COX I, II, III and IV, revealing consistent patterns across the neural retina and RPE. However, the central retina also draws on glycolysis as an energy source shown by the differential presence of lactate dehydrogenase and pyruvate dehydrogenase specifically expressed in the macular. Further, short wavelength sensitive cones (S-cones) may use glycolysis as their main energy source across the retina as they only express lactate dehydrogenase and not pyruvate dehydrogenase. This explains their distinct psychophysical characteristics which saturate prematurely compare to medium and long wavelength sensitive cones. That S-cones use glycolysis is reinforced by their reduced function in diabetes where declining insulin levels will restrict S-cones access to glucose.
Conclusions :
Methylglyoxal is a byproduct of glycolysis and this can promote advanced glycation end-products which are toxic. This process may contribute to age related attrition in the central retina and reduced S-cone function in ageing.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.