Abstract
In the past, the importance of serine to pathologic or physiologic anomalies was inadequately addressed. Omics research has significantly advanced in the last two decades, and metabolomic data of various tissues has finally brought serine metabolism to the forefront of metabolic research, primarily for its varied role throughout the central nervous system. The retina is one of the most complex neuronal tissues with a multitude of functions. Although recent studies have highlighted the importance of free serine and its derivatives to retinal homeostasis, currently few reviews exist that comprehensively analyze the topic. Here, we address this gap by emphasizing how and why the de novo production and demand for serine is exceptionally elevated in the retina. Many basic physiological functions of the retina require serine. Serine-derived sphingolipids and phosphatidylserine for phagocytosis by the retinal pigment epithelium (RPE) and neuronal crosstalk of the inner retina via D-serine require proper serine metabolism. Moreover, serine is involved in sphingolipid–ceramide balance for both the outer retina and the RPE and the reductive currency generation for the RPE via serine biosynthesis. Finally and perhaps the most vital part of serine metabolism is free radical scavenging in the entire retina via serine-derived scavengers like glycine and GSH. It is hard to imagine that a single tissue could have such a broad and extensive dependency on serine homeostasis. Any dysregulation in serine mechanisms can result in a wide spectrum of retinopathies. Therefore, most critically, this review provides a strong argument for the exploration of serine-based clinical interventions for retinal pathologies.
Highlights
In the past, the importance of serine to pathologic or physiologic anomalies was inadequately addressed
Considerable evidence has indicated that both the retinal pigment epithelium (RPE) and Müller cells of the inner retina have the requisite enzymes for serine biosynthesis
Besides the significant contribution of these two tissues to the serine pool of the entire retina, we established the role de novo serine synthesis plays in redox currency generation and in mitigating free radical stress for both the neural retina and RPE
Summary
Serine is a non-essential amino acid directly involved in cellular homeostasis, proliferation, and differentiation [1,2]. Serine uptake occurs either by delivery from the bloodstream or it can be synthesized by the anabolism of the glycolytic intermediate, 3-phosphoglycerate (3-PG) [4] in the retina (neural retina-RPE, Figure 1). The rate limiting step for serine biosynthesis is the reaction involving phosphoglycerate dehydrogenase (PHGDH), which converts 3-phosphoglycerate into phosphoserine. This is followed by the removal of the phosphate. Other an integral acid in multiple essential proteins, serineinvolved is essential It has than been being previously shownamino that the retina expresses high levels of all free enzymes in for generating cysteine, glycine, methionine, and sphingolipids [5]. The RPE appears to express even higher levels than the neural retina intermediates.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
