title: Reduction of enhanced rabbit intraocular pressure by instillation of pyroglutamic acid eye drops.
abstract: L-Pyroglutamic acid (PGA) is an endogenous molecule derived from l-glutamate. We demonstrate the effects of PGA on intraocular pressure (IOP) in experimentally induced ocular hypertension in rabbits. In the in vitro and in vivo transcorneal penetration studies, the PGA solution (PGA in saline) did not penetrate the rabbit cornea. On the other hand, the penetration of PGA was improved by the addition of zinc chloride and 2-hydroxypropyl-β-cyclodextrin (HPCD), and PGA penetration was enhanced with increasing HPCD concentration. Therefore, PGA solutions containing 0.5% zinc chloride and 5% or 10% HPCD (PGA/HPCD(5% or 10%) eye drops) were used to investigate the effects for IOP in this study. An elevation in IOP was induced by the rapid infusion of 5% glucose solution (15 mL/kg of body weight) through the marginal ear vein or maintaining under dark phase for 5 h. In the both models, the induced elevation in IOP was prevented by the instillation of PGA/HPCD eye drops, and the IOP-reducing effect enhanced with increasing HPCD concentration in the drops. Nitric oxide (NO) levels elevated in the aqueous humor following the infusion of 5% glucose solution, and this increase was also suppressed by the instillation of PGA/HPCD eye drops. In conclusion, the present study demonstrates that the instillation of PGA/HPCD eye drops has an IOP-reducing effect in rabbits with experimentally induced ocular hypertension, probably as a result of the suppression of NO production.
authors.affiliation: Faculty of Pharmacy, Kinki University, Higashi-Osaka, Osaka, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Ito
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nagai
authors.forename: Norio
authors.initials: N
authors.lastname: Okamoto
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Shimomura
authors.forename: Kunio
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Tanaka
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D066298:In Vitro Techniques; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009883:Ophthalmic Solutions; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits; D047392:beta-Cyclodextrins / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D009883:Ophthalmic Solutions; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D009569:Nitric Oxide; D011761:Pyrrolidonecarboxylic Acid