Abstract
Purpose :
Melatonin is a natural hormone whose receptors have been found in the ciliary epithelium of the mammalian eyes. The level of melatonin in the aqueous humor displays a diurnal variation, potentially contributing to the regulation of aqueous humor dynamics. However, it remains controversial whether melatonin plays a significant role in the modulation of aqueous humor secretion and thereby intraocular pressure. This study aims to determine the mechanistic actions of melatonin on aqueous humor secretion in porcine ciliary epithelium.
Methods :
Fresh porcine ciliary body epithelium was mounted in a modified Ussing-Zerahn-type chamber. The effects of melatonin, either in the presence or absence of inhibitor pretreatment, on both transepithelial electrical measurements and fluid movement across the ciliary epithelium were determined. The melatonin-mediated changes in solute movement from pigmented ciliary epithelial (PE) to non-pigmented ciliary epithelial (NPE) cells was also monitored by Lucifer Yellow dye transfer.
Results :
At 100µM, melatonin increased the short-circuit current (Isc) by 38±6% (N=6, p<0.001) and 40±9% (N=11, p<0.001) when administrated to both sides (i.e. stromal and aqueous sides) and aqueous side of the preparations, respectively. The stimulation of Isc was abolished by the pretreatment of either non-selective gap junction blocker heptanol or Cl- channel blocker niflumic acid. Likewise, addition of melatonin to the aqueous surface caused an increase in fluid secretion by 50% across the intact ciliary epithelium (N=11, p<0.01), as reflected by a significant increase (~50-60%) in dye transfer from PE to NPE cells across the PE-NPE cell couplets. Pretreatment of MT1/MT2 antagonist luzindole significantly enhanced the melatonin-mediated Isc stimulation (N=9, p<0.001) while pretreatment of selective MT3 antagonist prazosin to the aqueous side abolished the Isc stimulation (N=10, p>0.05).
Conclusions :
Melatonin enhances Cl- and fluid secretion across the porcine ciliary epithelium. The melatonin-induced Cl- and fluid movement is possibly mediated by MT3 receptors on NPE cells.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.