Amine-responsive Rhodopsin-like GPCRs in ocular pathology: mechanistic associations, candidate biomarkers, and therapeutic potential

Rhodopsin-like G protein-coupled receptors (GPCRs) play a pivotal role in ophthalmic pathologies, and recent studies have substantially advanced our understanding of their underlying molecular mechanisms. Amine-responsive Rhodopsin-like GPCRs (ARh-GPCRs), encompassing adrenoceptors, dopamine receptors, muscarinic acetylcholine receptors, histamine receptors, serotonin receptors, melatonin receptors, and trace amine-associated receptors, are involved in a variety of ocular pathological processes and have emerged as key therapeutic targets. Elucidating their functional roles, alongside those of their ligands and downstream signaling macromolecules, holds considerable potential for the development of candidate biomarkers for early diagnosis, disease classification, prognostication, and predicting treatment response in specific ocular disorders. Despite significant progress, a comprehensive integration of their dual candidate biomarker-therapeutic roles across diverse ocular disorders remains largely unexplored. This narrative review summarizes and critically integrates current evidence on the regulatory roles and therapeutic potential of these receptors in ocular pathologies, with particular attention to their mechanistic involvement, candidate biomarker potential, and therapeutic relevance. Furthermore, we summarize the current research limitations and propose future directions to enhance the understanding of their molecular mechanisms, ultimately facilitating the development of precise diagnostic and therapeutic strategies.