Intraocular penetration of topically applied agents and the conditions for their penetration in human eyes and glaucoma-model animal eyes

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591740
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: The University of Tokyo
• Principal Investigator: TOMIDOKORO Atsuo The University of Tokyo, Faculty of Medicine, Lecturer, 医学部付属病院, 講師 (80227628)
• Co-Investigator(Kenkyū-buntansha): KUNIMATSU Shiho The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (80301563) ; MATSUO Hiroshi The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (60332615)
• Project Period (FY): 2004 – 2005
• Keywords: retinal vessel / endothelin / glaucoma / ocular circulation

Research Abstract

1) Effects of various antiglaucoma topical agents on retinal vessels contracted with intravitreous injection of endothelin or phenylephrine.
In anesthetized rabbits, endothelin was injected intravenously, and the changes in the diameter of retinal blood vessels were serially evaluated on fundus photographs. Topically applied prostaglandin-related antiglaucoma agents, such as latanoprost travoprost, and unoprostone on its reaction of the retinal vessels were found to significantly reduce the contraction of retinal vessels, suggesting that the topically applied agents could reach the retina or optic nerve with pharmacologically effective concentration.
2) Effects of phenylephrine on human ocular circulation.
In aged humans, the central retina artery circulation indices determined using the color Doppler imaging (CDI), IOP, blood pressure, and pulse rate were measured before and after 4 serial instillations at 30-minute intervals of unilateral phenylephrine. As the results, IOP in the phenylephrine-treated eyes significantly increased, while the CDI indices, blood pressure, and pulse rate did not.
3) Autoregulation of ocular circulation and the effects of topically applied agents on it in glaucoma model animal eyes with high intraocular pressure.
In cynomolgus monkey eyes, glaucoma model with high intraocular pressure were prepared with the laser irradiation onto the trabecular meshwork. Intraocular pressure was significantly increased and maintained for more than several months. In these model eyes and the contralateral normal eyes, autoregulation in the optic nerve head against an acute rise in intraocular pressure was found using the laser speckle method. Antiglaucoma prostaglandin-related agents increased the ocular circulation in the both glaucoma-model and normal eyes, but the profile of the reaction looked different between those eyes.