Energy metabolism in rod and cone photoreceptors and its connection to disease

Gabriele Wögenstein

Already 100 years ago Otto Warburg discovered that energy metabolism in the retina differs from other tissues. He observed in the presence of oxygen the retina produces lactate. Otherwise, this phenomenon (Warburg effect) was only observed in cancer cells. The production of lactate suggests that the retina performs aerobic glycolysis and bypasses oxidate phosphorylation. 

Many studies have established that the retina is metabolically highly active and requires large amounts of oxygen for energy production. Therefore, any disturbances in oxygen availability or energy metabolism may have an influence on cell survival. Many ophthalmologic diseases including diabetic retinopathy and age-related macular degeneration (AMD) are linked to mitochondrial impairment and therefore deficits in energy production. Additionally, several studies link hypoxic response to energy production and changes in energy metabolism to disease onset and/or progression. 

Therefore, we aim to better understand energy metabolism in photoreceptors and the cellular mechanism behind the observations from Otto Warburg. To achieve this, we use two-photon microscopy to image genetically encoded nanosensors allowing us to measure the levels of ATP, glucose and lactate in individual cell types. We are especially interested in potential differences between rod and cone photoreceptors and between photoreceptors and neurons of the inner retina. We hopw that this approach will allow us to gain a better understanding of energy metabolism in photoreceptor cells in physiological and pathophysiological conditions.