The Symbiotic Relationship between the Neural Retina and Retinal Pigment Epithelium Is Supported by Utilizing Differential Metabolic Pathways

Abstract

The neural retina and retinal pigment epithelium (RPE) maintain a symbiotic metabolic relationship, disruption of which leads to debilitating vision loss. The current study was undertaken to identify the differences in the steady-state metabolite levels and the pathways functioning between bona fide neural retina and RPE. Global metabolomics and cluster analyses identified 650 metabolites differentially modulated between the murine neural retina and RPE. Of these, 387 and 163 were higher in the RPE and the neural retina, respectively. Further analysis coupled with transcript and protein level investigations revealed that under normal physiological conditions, the RPE utilizes the pentose phosphate (>3-fold in RPE), serine (>10-fold in RPE), and sphingomyelin biosynthesis (>5-fold in RPE) pathways. Conversely, the neural retina relied mostly on glycolysis. These results show how the RPE and the neural retina have acquired an efficient, complementary and metabolically diverse symbiotic niche to support each other's distinct functions.

Flavins Act as a Critical Liaison Between Metabolic Homeostasis and Oxidative Stress in the Retina

“…The whole eye as an organ harbors arguably the highest level of riboflavin in the whole body (normalized to total protein content), and even though the cornea takes the major share of this, but it uses riboflavin mostly for structural purposes ( Batey and Eckhert, 1990 , 1991 ; Batey et al, 1992 ). The RPE and closely followed by the NR have the highest concentration of both the functional forms of riboflavin, FAD and FMN, and they are used critically as metabolic cofactors and free radical scavengers ( Sinha et al, 2018 , 2020b ). It has been well elucidated that the glutathione based free radical scavenging system is highly dependent on flavins ( Beutler, 1969 ).…”

Retinal pigment epithelium and age‐related macular degeneration: A review of major disease mechanisms

“…7 Some important roles of RPE include the daily phagocytosis of photoreceptor outer segments (POS), secretion of neutrophic factors required to stabilize the neural retina and scavenging for damaged ROS. 7,8 While photoreceptors take part in the phototransduction cascade through isomerisation of 11-cis retinal to all-trans retinal, the process of recycling all-trans retinal back to 11-cis retinal is supported by the RPE, making RPE an integral part of the visual cycle. 7 Additionally, a single RPE cell interacts with several photoreceptors, making the RPE a highly metabolically active tissue.…”

“…7 Additionally, a single RPE cell interacts with several photoreceptors, making the RPE a highly metabolically active tissue. 8 The AMD spectrum spans early-stage AMD, during which drusen, pigment epithelial detachment (PED) and vitelliform lesions are observed, to late stage AMD, with choroidal neovascularization (CNV, neovascular AMD) or geographic atrophy (GA). Clinically, patients with early-stage AMD commonly present with drusen (lipid) deposits in the space between the basal lamina of the RPE and Bruch's membrane, the innermost layer of the choroid.…”

“…The RPE is a highly active tissue due to the tightly regulated support it offers to the neural retina 7 . Some important roles of RPE include the daily phagocytosis of photoreceptor outer segments (POS), secretion of neutrophic factors required to stabilize the neural retina and scavenging for damaged ROS 7,8 . While photoreceptors take part in the phototransduction cascade through isomerisation of 11‐ cis retinal to all‐ trans retinal, the process of recycling all‐ trans retinal back to 11‐ cis retinal is supported by the RPE, making RPE an integral part of the visual cycle 7 .…”

“…While photoreceptors take part in the phototransduction cascade through isomerisation of 11‐ cis retinal to all‐ trans retinal, the process of recycling all‐ trans retinal back to 11‐ cis retinal is supported by the RPE, making RPE an integral part of the visual cycle 7 . Additionally, a single RPE cell interacts with several photoreceptors, making the RPE a highly metabolically active tissue 8 …”