Effects of Some Opiates and Opioid Peptide Eyedrops on Ocular Melatonin Regulation in Rabbits

Abstract

Levels of melatonin in rabbit eye tissues were detected by radioimmunoassay. Solutions of met-enkephalin, leu-enkephalin, α-endorphin and β-endorphin were given topically. Met-Enkephalin and α-endorphin lowered levels of melatonin in the iris, iris root-ciliary body, retina and choroid; leu-enkephalin raised levels in the retina and lowered them in other tissues. β-Endorphin only lowered levels in the iris root-ciliary body. DAGO (a μ agonist) given i.v. lowered levels of melatonin in the iris, iris root-ciliary body and retina. The δ and σ agonists given i.v. only lowered levels in the iris root-ciliary body, and a k agonist given i.v. raised levels in the ciliary body. No opiate binding sites could be detected in the rabbit iris or iris root-ciliay body for any class of receptor. Our data suggest opioids may be useful for treating glaucoma.

Influence of the Hypothalamic Arcuate Nucleus on Intraocular Pressure and the Role of Opioid Peptides

“…Reduction of the aqueous flow rate through activation of μ-3 opioid receptors and increased production of NO has been reported to be involved morphine's action [10]. The μ agonist DAMGO and the δ agonist DPDPE have been shown to deplete melatonin levels in the ciliary body, an action that causes IOP to fall [12]. μ and δ agonists have also been shown to decrease the excitatory post-synaptic current in rat brain slices [11].…”

Functional Identification of a Novel Transport System for Endogenous and Synthetic Opioid Peptides in the Rabbit Conjunctival Epithelial Cell Line CJVE

“…There is evidence for the clinical utility of opiates in the treatment of a variety of ocular diseases such as glaucoma (25, 26), eye pain (27), and ocular infection of herpes simplex virus (HSV-1) (28). The functional identification of a robust transport process for opioid peptides in conjunctival epithelial cells may provide a rationale for targeting the conjunctiva as an effective delivery route for these peptides.…”

Effects of Melatonin and Haloperidol Given via Vortex Vein on the Intraocular Pressure

“…Peptides, particularly endogenous opiates, are promising candidates. Opioids al ter IOP [21][22][23] and pupillary diameter, al though the effects of any single opioid are complex [23] and probably represent the net effect of a drug acting at multiples sites.…”

“…Alterations in intraocular pressure arc observed after opiates [21][22][23], Opioid neuro peptides are present in ocular tissues [24]; however, they may alter IOP through a central nervous system or a ganglionic site of action rather than acting locally. Knowing the neuro transmitters regulating ocular melatonin lev els will greatly expedite the development of drugs which alter melatonin levels and pre sumably alter IOP.…”