Retinal energy metabolism in health and glaucoma

Energy metabolism refers to the processes by which life transfers energy to do cellular work. The retina's relatively large energy demands make it vulnerable to energy insufficiency. In addition, evolutionary pressures to optimize human vision have been traded against retinal ganglion cell bioenergetic fragility. Details of the metabolic profiles of the different retinal cells remain poorly understood and are challenging to resolve. Detailed immunohistochemical mapping of the energy pathway enzymes and substrate transporters has provided some insights and highlighted interspecies differences. The different spatial metabolic patterns between the vascular and avascular retinas can account for some inconsistent data in the literature. There is a consilience of evidence that at least some individuals with glaucoma have impaired RGC energy metabolism, either due to impaired nutrient supply or intrinsic metabolic perturbations. Bioenergetic-based therapy for glaucoma has a compelling pathophysiological foundation and is supported by recent successes in animal models. Recent demonstrations of visual and electrophysiological neurorecovery in humans with glaucoma is highly encouraging and motivates longer duration trials investigating bioenergetic neuroprotection.