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M.A. McLaughlin, D.E. Brooks, D. Earnest, L. Klekar, H. Sapp, I.–H. Pang, M. Hellberg, W.F. Holt; ANP and CNP Effects on IOP in Rabbits and Monkeys . Invest. Ophthalmol. Vis. Sci. 2006;47(13):412.
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To evaluate atrial natriuretic peptide (ANP) and C–type natriuretic peptide (CNP) ocular injection effects on intraocular pressure (IOP) in rabbits and to determine IOP effects of CNP in nonhuman primates.
The peptides were injected intracamerally (IC) or intravitreally (IVT) in Dutch belted (DB) rabbits, cynomolgus monkeys, and rhesus monkeys with unilateral trabeculoplasty resulting in ocular hypertension. Dosing was unilateral drug with contralateral vehicle. Rabbits were anesthetized for IC injection; monkeys for both IC and IVT injection. IOP was measured at intervals post–dose by applanation tonometry. Monkeys were lightly anesthetized for tonometry; rabbits were fully conscious. IVT data were calculated as change from same day baseline (time=0); IC data as difference from vehicle eyes at the same time point.
IC: ANP (10, 20 µg) and mini–ANP (10, 30, 100 µg) did not alter IOP in DB rabbit (n=7–10, p>0.05). CNP (10 µg) did not lower IOP in DB rabbits (n=10) or cynomolgus monkeys (n=4, p=0.2). IVT: ANP (40 µg) and mini–ANP (100 µg) lowered IOP a maximum of 30.9% and 15% respectively in DB rabbits (n=7–9, p=0.001). CNP gave a dose response effect in the DB rabbit with maximum IOP reduction of 25% (1 µg, n=7, p=0.01), 43% (10 µg, n=10, p=0.001), and 47% (50 µg, n=6, p=0.001). Duration of IOP lowering increased with dose; no effect lasted to 48 hours. CNP (50 µg) in the rhesus monkey lowered IOP 20% in lasered eyes (n=6, p=0.05) compared to baseline.
The natriuretic peptides and their receptors have been speculated to be involved in the regulation of IOP based on receptor presence in ocular tissues and IOP studies in rabbits, monkeys, and humans. We did not reproduce IOP lowering with intracameral ANP or CNP in rabbits. Intravitreal ANP and CNP lower IOP in both rabbit and lasered monkey. Duration of effect appears dose–related.
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