Exp Eye Res. 2026 Apr 20:111033. doi: 10.1016/j.exer.2026.111033. Online ahead of print.
ABSTRACT
Amino acid metabolism serves as a central hub linking retinal energy supply, neurotransmission, and cell signaling, which is critical for maintaining retinal structure and function. This review summarizes the molecular mechanisms by which abnormal amino acid metabolism contributes to retinal diseases. The major mechanisms include: 1) excitotoxicity caused by disruption of glutamate-glutamine cycle; 2) mitochondrial oxidative stress and epigenetic changes due to accumulation of branched-chain and sulfur-containing amino acids; 3) remodeling of immune microenvironment due to altered tryptophan and arginine metabolism; 4) neurotoxic lipid production and signaling imbalance resulting from serine and glycine deficiency. Clinically, we highlight the emerging roles of intraocular fluid metabolomics-based liquid biopsy and artificial intelligence-assisted multimodal imaging in early diagnosis and molecular classification. We further summarize emerging treatment approaches, including metabolic substrate supplementation, interventions targeting key enzymes and transporters, and development of responsive nanodelivery systems. Overall, restoration of amino acid metabolic homeostasis represents a promising strategy for the prevention and treatment of retinal diseases.
PMID:42019874 | DOI:10.1016/j.exer.2026.111033