Muscarinic Acetylcholine Receptors in the Retina-Therapeutic Implications

Muscarinic acetylcholine receptors (mAChRs) belong to the superfamily of G-protein-coupled receptors (GPCRs). The family of mAChRs is composed of five subtypes, M₁, M₂, M₃, M₄ and M₅, which have distinct expression patterns and functions. In the eye and its adnexa, mAChRs are widely expressed and exert multiple functions, such as modulation of tear secretion, regulation of pupil size, modulation of intraocular pressure, participation in cell-to-cell signaling and modula-tion of vascular diameter in the retina. Due to this variety of functions, it is reasonable to assume that abnormalities in mAChR signaling may contribute to the development of various ocular diseases. On the other hand, mAChRs may offer an attractive therapeutic target to treat ocular diseases. Thus far, non-subtype-selective mAChR ligands have been used in ophthalmology to treat dry eye disease, myopia and glaucoma. However, these drugs were shown to cause various side-effects. Thus, the use of subtype-selective ligands would be useful to circumvent this problem. In this review, we give an overview on the localization and on the functional role of mAChR subtypes in the eye and its adnexa with a special focus on the retina. Moreover, we describe the pathophysiological role of mAChRs in retinal diseases and discuss potential therapeutic approaches.