Abstract
The light‐sensitive photoreceptors in the retina are extremely metabolically demanding and have the highest density of mitochondria of any cell in the body. Both physiological and pathological retinal vascular growth and regression are controlled by photoreceptor energy demands. It is critical to understand the energy demands of photoreceptors and fuel sources supplying them to understand neurovascular diseases. Retinas are very rich in lipids, which are continuously recycled as lipid‐rich photoreceptor outer segments are shed and reformed and dietary intake of lipids modulates retinal lipid composition. Lipids (as well as glucose) are fuel substrates for photoreceptor mitochondria. Dyslipidemia contributes to the development and progression of retinal dysfunction in many eye diseases. Here, we review photoreceptor energy demands with a focus on lipid metabolism in retinal neurovascular disorders.
Highlights
The light-sensitive photoreceptors in the retina are extremely metabolically demanding and have the highest density of mitochondria of any cell in the body
Continuous shedding of “used” outer segments containing lipids damaged by light and oxidation is critical for the maintenance of normal retinal function (Fliesler & Anderson, 1983) perhaps as a fuel source scavenged by retinal pigment epithelium (RPE)
Other lipid fuel sources may be serum lipids processed by Muller glial cells, and lipids synthesized at a high rate in the inner segments (Wang et al, 2005; Kevany & Palczewski, 2010; Casson et al, 2013)
Summary
+H C C (LCPUFA, ~45% of total phospholipids), saturated fatty acid (SFA, ~37% of total phospholipids), and monounsaturated fatty acid (MUFA, ~10% of total phospholipids; Schnebelen et al, 2009). Transcriptional control of retinal cell functions The retina contains more than 10 different cell types that contribute uniquely to phototransduction (Fig 2B), requiring a highly individualized gene expression pattern. Beside identity markers associated with specialized functions (like phototransduction in photoreceptors; Fig 3B), different retinal cells regulate specific metabolic genes at the transcriptional level to perform certain functions. Caution is required when analyzing transcriptomic data from rod photoreceptors, as this cell type has low basal gene expression (Macosko et al, 2015), which is correlated with a uniquely closed chromatin architecture compared to cones (Hughes et al, 2017). Dyslipidemia is characterized by an abnormal circulating lipid profile including triglycerides, cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), or polyunsaturated fatty acids. Percentage of FAs in total amount of retinal phospholipids ~ 45% LCPUFA ~ 37% SFA ~10% MUFA Schnebelen et al, 2009.
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