Acute effects of glaucoma medications on rat intraocular pressure.
The rat has been used increasingly in glaucoma research, but many aspects regarding the regulation of its intraocular pressure (IOP) are still unknown. For example, it is not clear whether glaucoma medications can lower IOP in the rat similarly to human. This information will be valuable in evaluating this animal model for its usefulness in predicting drug effects in patients. Hence, we tested the acute IOP effects of selected glaucoma drugs topical administered onto the rat eye. In these studies, IOP was measured using the Tono-Pen XL tonometer. After a correlation between the IOP reported by the Tono-Pen and actual IOP was established, IOP measurements were obtained in slightly sedated adult rats. Effects of glaucoma medications were tested in two groups of animals. One group (12 h/L) was housed in a 12-h/12-h light/dark cycle. The other (24 h/L) was housed under constant light. Exposure of the animals to constant light increased their basal IOP from 20.5+/-0.6 mmHg (mean+/-S.E.M., n=12) to 32.0+/-0.5 mmHg. At 3 h after topical administration, Betoptic S lowered IOP by 4.3+/-1.7 mmHg (n=6) and 3.7+/-0.3 mmHg (n=6) in the 12 and 24h/L rats, respectively. Pilocarpine did not affect rat IOP. Xalatan produced a biphasic response in the rat. At 3h after topical administration, it increased IOP by 7.9+/-1.4 and 7.0+/-1.0 mmHg in the 12 and 24 h/L rats, respectively. By the next day, it decreased IOP by 3.0+/-1.0 and 6.0+/-0.8 mmHg in the 12 and 24 h/L rats, respectively. The IOP-enhancing effect of Xalatan was dose-dependent. The present study indicates that IOP responses of the rat to different pharmacological agents are not identical to those of the human. In the rat, Betoptic S, but not pilocarpine, lowered IOP. Xalatan initially increased then decreased IOP.
Pang
Iok-Hou
IH
Alcon Research, Ltd, Fort Worth, TX 76134, USA. iok-hou.pang@alconlabs.com
Wang
Wan-Heng
WH
Clark
Abbot F
AF
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015784:Betaxolol / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D008297:Male; D010862:Pilocarpine / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D017208:Rats, Wistar; D013045:Species Specificity; D014065:Tonometry, Ocular / Q000295:instrumentation
D000959:Antihypertensive Agents; D011461:Prostaglandins F, Synthetic; D010862:Pilocarpine; D000077338:Latanoprost; D015784:Betaxolol