Comparison of glucose metabolism in human macula and peripheral retina

Abstract

Purpose : Glucose Metabolism plays a pivotal role in maintaining the normal function of the neural retina. Dysfunction of glucose metabolism is a feature of several macular diseases. However, whether glucose metabolism in the macula is different from the rest of the retina is still not clear. We have established a unique human neuroretinal explant system to study the differences in glucose metabolism between the human macula and peripheral retina.

Methods : C¹³ glucose was incubated with human macular explants from six donors for 2 and 4 hours. Downstream metabolites were extracted from the cultured neuroretina and analysed by Gas Chromatography Mass Spectroscopy. Results were compared with samples of peripheral retina of the same eye. We also studied the differential expression levels of key enzymes in glucose metabolism from the macula and peripheral retina by western blot.

Results : We found significant differences in the proportions of C¹³ glucose labeled metabolites between the macula and peripheral neuroretina. The biosynthesis rates of lactate and pyruvate were significantly higher, but phosphoenolpyruvate was significantly lower, in the macula than in the peripheral retina. This was consistent with the observation of significantly higher protein expression levels of Pyruvate Kinase M2 and Lactate Dehydrogenase A in the macula compared with the peripheral retina. We also found the biosynthesis of major metabolites in the tricarboxylic acid (TCA) cycle, α-ketoglutarate, glutamate, and succinate, were significantly lower in macular than peripheral neuroretina.

Conclusions : The human macula metabolises glucose differently than the rest of the retina. We found that glucose was metabolized more by glycolysis in the macula and more by oxidative phosphorylation in the peripheral retina. This difference may explain at least in part why the macula is more susceptible to disease than the rest of the retina.

This is a 2020 ARVO Annual Meeting abstract.