Apraclonidine Protection of the Blood-Aqueous Barrier from Traumatic Break-Down

Abstract

This study investigated the effects of apraclonidine hydrochloride 1% eye drops on blood-aqueous barrier in 108 pigmented rabbits. The effects of pretreatment with dapiprazole and yohimbine, and a comparison with clonidine 0.125% eye drops are also reported. The disruption of blood-aqueous barrier was obtained by argon laser burning of the iris. The degree of permeability of the barrier was deduced by the amount of proteins in aqueous humor 60 min after laser application. Intraocular pressure and pupil diameter were also studied. Protein content in aqueous humor was 0.72 +/- 0.26 g/l in control rabbits that did not receive any treatment; 5.98 +/- 4.23 g/l in rabbits instilled with placebo eye drops and treated by laser burning of iris; 0.43 +/- 0.25 g/l in rabbits that received apraclonidine eye drops prior to laser burning; 2.19 +/- 1.3 g/l in rabbits that received apraclonidine eye drops immediately after laser application; 0.35 +/- 0.08 g/l in rabbits that received apraclonidine 1% eye drops both before and after laser application. Rabbits treated with clonidine 0.125% had a protein content in aqueous humor of 5.45 +/- 2.08 g/l after laser application. Dapiprazole 0.5% eye drops prior to apraclonidine led to a protein content in aqueous humor of 1.93 +/- 2.13 g/l; yohimbine 0.3% eye drops prior to apraclonidine led to a protein content of 0.70 +/- 0.40 g/l. Protein content in aqueous humor was 0.93 +/- 0.36 g/l, 0.82 +/- 0.899 g/l and 1.68 +/- 1.39 g/l in rabbits treated with yohimbine 0.3, 0.6 and 1.2 mg/kg i.v. and then with apraclonidine 1% eye drops. In one group of rabbits, the penetration into the aqueous humor of Evans blue injected intravenously was also studied. Evans blue content in aqueous humor was 0.03 +/- 0.08 mg/100 ml in control rabbits; 0.92 +/- 0.53 mg/100 ml in placebo rabbits treated by laser; and 0.28 +/- 0.19 mg/100 ml in apraclonidine rabbits treated by laser. Apraclonidine eye drops led to a decrease in IOP and prevented IOP rise following argon laser application. Placebo treated rabbits had a 20% increase in IOP following laser application. Apraclonidine-treated eyes showed mydriasis and blanching of the conjunctiva. These effects were not affected by pretreatment with dapiprazole or yohimbine. In these experiments, the treatment with apraclonidine 1% eye drops completely protected the blood aqueous barrier from the disruption caused by laser burning of the iris. The protection was less effective when apraclonidine was applied after laser burnings.

Effects of Topical Clonidine on Prostaglandin-E₂-Induced Aqueous Flare Elevation in Pigmented Rabbits

“…Bonomi et al [14] reported that pretreatment with apraclonidine 1% eyedrops completely protected the blood-aqueous barrier from disruption caused by laser burning of the iris. Our findings using PGE 2 and clonidine were similar to the data using laser burning and apraclonidine reported by Bonomi et al [14]. Anti-inflammatory actions of clonidine have previously been reported by Holsapple et al [12].…”

“…Systemic administration of clonidine significantly reduced the acute inflammatory swelling of the rat paw produced by carrageenin, histamine and serotonin [12]. Topical apraclonidine (paminoclonidine) reduced the intraocular pressure rise and elevation of the aqueous humor protein following YAG and argon laser irradiation to the rabbit iris [13,14]. We have previously reported that transcorneal diffusion of prostaglandin E 2 (PGE 2 ) using a glass cylinder produced aqueous flare elevation in pigmented rabbits [15].…”

Aqueous Humor Dynamics in Anesthetized Rats Infused with Intracameral Apraclonidine

“…These features render the rat a potentially useful surrogate to study IOP control mechanisms and actions of antiglaucoma drugs. Several models use techniques that raise IOP by physically damaging ocular structures, such as laser destruction of the trabecular meshwork, or cauterization of episcleral veins [5,7,21]. Such models are useful, as the elevated IOP can be studied in the conscious state over time, although intermittent, indirect measurements of IOP are used.…”

“…Clonidine, however, causes cardiovascular effects after systemic absorption from the eye [1]. Apraclonidine (AP, p-aminoclonidine) is more commonly used topically for glaucoma, as it penetrates the cornea and blood-brain barrier to a lesser extent and, thus, has fewer adverse systemic effects [3][4][5]. AP is effective in animal models of elevated IOP as well as glaucoma in humans.…”