Endothelin‐1 effects on aqueous humor dynamics in monkeys

Abstract

ABSTRACT.Purpose: To report data showing no effect of endothelin-1 on aqueous humor formation and total outflow facility in the cynomolgus monkey, in contrast to the enhancement of outflow facility in monkeys and the suppression of aqueous humor flow in rabbits previously reported by others. Methods: Living monkeys received, unilaterally: (i) intracameral endothelin-1 (10 ml bolus, or 2ml or 4ml exchange; final intracameral concentration 1 or 10 nM) with total outflow facility measured for up to 1 hr post-treatment by twolevel constant pressure perfusion, and (ii) intravitreal endothelin-1 (20 ml, final intravitreal concentration 0.1 or 1 mM) with aqueous humor flow measured by scanning fluorophotometry for 5 hr starting 12 hr post-treatment. Contralateral eyes received vehicle. Results: Endothelin-1 had no effect on total outflow facility or aqueous humor flow with any of the methods described. Conclusion: Endothelin-1 seems have a variable effect on aqueous humor dynamics within and between species.

Pharmacological and Functional Characterization of Endothelin Receptors in Bovine Trabecular Meshwork and Ciliary Muscle

“…ET-1 has been found to cause contraction of vascular smooth muscle and pericytes and has therefore been suggested to play a role in retinal and choroidal blood fl ow regulation [5,6] . Furthermore ET-1 has been shown to play an important role in the regulation of the outfl ow pathway in the anterior segment of the bovine [9,14] and primate eye [15,16] .…”

Effect of Fluoxetine on Intraocular Pressure in the Rabbit

“…Recent autoligand binding, autoradiographic and molecular biological data have now provided suf®cient information to con®rm that in ciliary processes at least three types of serotonin receptors are present, namely 5-HT 1A , 5-HT 7 and 5-HT 2A/2C receptors (Tobin et al, 1988;Osborne and Chidlow, 1996). Activation of 5-HT 1A receptors with speci®c agonists causes a reduction of the IOP (Chu et al, 1996;Millar et al, 1996;Wang et al, 1997), just as the blockage of 5-HT 2 receptors with speci®c antagonists also reduces IOP (Chang, Burke and Potter, 1985;Mano et al, 1995). This could explain the controversial results reported after topical application of serotonin to the rabbit eye wherein both a decrease in IOP (Krootila et al, 1987) and an increase (Meyer-Bothling et al, 1993) have, in fact, been demonstrated.…”

Endothelin-A Receptor Antagonist BQ-485 Protects against Intraocular Pressure Spike Induced by Laser Trabeculoplasty in the Rabbit

“…The endothelin receptors (ET A and ET B ) are abundant in the uveal tissues and probably have an important role in the regulation of aqueous humour outflow [11, 15, 16, 20]. The effect of ET-1 on the ciliary muscle and the trabecular meshwork contractility is concentration dependent [15, 17]. It has also been shown that aqueous humour ET-1 concentration is higher in high-pressure primary open angle glaucoma than in normal pressure glaucoma [22]or in non-glaucomatous eyes [21, 23].…”

“…The human and the rabbit trabecular meshwork both contain contractile elements which are strongly constricted by ET-1 via endothelin A (ET A ) receptor activation [15, 16]. Since the ET-1-induced constriction of the trabecular meshwork probably leads to an acute decrease of outflow and a secondary IOP elevation [15, 16], the role of laser-induced ET-1 release in the development of the post-laser IOP spikes seems to be plausible, even if the degree of the outflow reduction may differ in different species [17]. …”