Regional and tissue-specific metabolic differences in human neural retina and RPE/choroid

The human retina, along with its underlying retinal pigment epithelium and choroid (RPE/choroid), operates as an interdependent metabolic system. However, the specific metabolic differences between the cone-rich macula and rod-rich peripheral regions remain unknown. Employing targeted metabolomics, researchers quantified 133 metabolites from paired macular and peripheral neural retina and RPE/choroid explants derived from human donor eyes. Distinct metabolic distinctions were found between different retinal regions and tissues.

The macula exhibited metabolic characteristics associated with heightened glycolytic activity, elevated NADH availability, and greater quantities of neurotransmitter-associated metabolites N-acetyl-aspartate (NAA) and N-acetyl-aspartyl-glutamate (NAAG), indicating increased energetic and neuronal activity. In contrast, peripheral RPE/choroid displayed higher levels of the flavin cofactor FAD, along with NAD-related metabolites such as NAD, NADP, and NAAD.

Furthermore, comparisons between the neural retina and RPE/choroid revealed that the neural retina primarily focuses on energy production and neurotransmission, while the RPE/choroid is involved in cofactor metabolism, nucleotide salvage, and lipid metabolism. These observations suggest metabolic coupling between the neural retina and RPE/choroid. The macula's metabolic profile, characterized by high energetic demand, may offer a potential metabolic rationale for its susceptibility to macular diseases.