Regulation of Aqueous Humor Secretion by Melatonin in Porcine Ciliary Epithelium

Secretion of melatonin, a natural hormone whose receptors are present in the ciliary epithelium, displays diurnal variation in the aqueous humor (AH), potentially contributing to the regulation of intraocular pressure. This study aimed to determine the effects of melatonin on AH secretion in porcine ciliary epithelium. The addition of 100 µM melatonin to both sides of the epithelium significantly increased the short-circuit current (Isc) by ~40%. Stromal administration alone had no effect on the Isc, but aqueous application triggered a 40% increase in Isc, similar to that of bilateral application without additive effect. Pre-treatment with niflumic acid abolished melatonin-induced Isc stimulation. More importantly, melatonin stimulated the fluid secretion across the intact ciliary epithelium by ~80% and elicited a sustained increase (~50-60%) in gap junctional permeability between pigmented ciliary epithelial (PE) cells and non-pigmented ciliary epithelial (NPE) cells. The expression of MT₃ receptor was found to be >10-fold higher than that of MT₁ and MT₂ in porcine ciliary epithelium. Aqueous pre-treatment with MT₁/MT₂ antagonist luzindole failed to inhibit the melatonin-induced Isc response, while MT₃ antagonist prazosin pre-treatment abolished the Isc stimulation. We conclude that melatonin facilitates Cl^- and fluid movement from PE to NPE cells, thereby stimulating AH secretion via NPE-cell MT₃ receptors.