Effects of latanoprost on rodent intraocular pressure Shahid Husain a , N. Andy Whitlock b , Dennis S. Rice b , Craig E. Crosson a, * a Hewitt Laboratory of the Ola B. Williams Glaucoma Center, Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA b Lexicon Genetics, The Woodlands, TX, USA Received 11 May 2006; accepted in revised form 5 August 2006 Available online 6 October 2006 Abstract The aim of the present study was to evaluate the effects of the prostaglandin F 2a analog, latanoprost, on the intraocular pressure (IOP) in rodent eyes. Rodents have been increasingly used in glaucoma research; however, conflicting results regarding the actions of prostaglandins on rodent IOP have been published. In Wistar rats, a single dose of latanoprost (60 ng) produced a biphasic change in IOP: an initial rise in pressure (2.1  0.7 mmHg) peaking at 2 h, followed by a prolonged hypotension with a peak reduction in IOP (5.2  0.7 mmHg) at 5 h. Both the hyper and hypotensive actions of latanoprost were dose-related with ED 50 values of 108 and 5.2 ng, respectively. These responses were antagonized by pretreatment with 4% pilocarpine. In Brown Norway rats and C57BL/6 mice, a single dose of latanoprost also produced a biphasic response in IOP with an initial rise in pressure peaking between 1 and 2 h, followed by prolonged hypotension from 4 to 8 h. These results demonstrate that in rodents the IOP response to topical latanoprost is characterized by an initial hypertension followed by a prolonged hypotension. This pro- longed hypotension is similar to that measured in monkeys and humans. Taken together, these results support the idea that rodents can serve as in vivo models to study the actions of ocular hypotensive agents, such as prostaglandins. Ó 2006 Elsevier Ltd. All rights reserved. Keywords: rat; mouse; intraocular pressure; latanoprost; glaucoma 1. Introduction Glaucoma is one of the leading causes of blindness in the United States and around the world. It is characterized by the progressive loss of vision and optic disc cupping. Elevated intraocular pressure (IOP) is considered a primary risk factor for the initiation and progression of glaucomatous optic neu- ropathy (Leske, 1983). Reduction in IOP has been shown to delay the onset and slow the rate of progression of irreversible blindness in glaucoma (AGIS Investigators, 2000). Identifying the factors that lead to elevated IOP and optic nerve damage, as well as the new treatment modalities, requires good animal models. Recently, rats and mice have become important models for studying glaucoma due to the increasing availabil- ity of transgenic animals and the cost-effectiveness of working with these smaller species (Goldblum and Mittag, 2002). In addition, rodents share similar anatomical (Daimon et al., 1997; van der Zypen, 1977) and developmental (Nucci et al., 1992; Reme et al., 1983) characteristics in the anterior seg- ment, especially in the aqueous outflow pathway, with those of the human. Therefore, aqueous humor dynamic studies in rodents may be more predictive of the response in humans, than those of other non-primate laboratory animals. Topical application of prostaglandin F 2a analogs has been shown to significantly reduce IOP in humans (Alm, 1995; Camras, 1996) and primates (Camras and Bito, 1981; Gabelt and Kaufman, 1990); however, conflicting reports have been published on the IOP responses in rodents. Initial studies in mice found that topical administration of the FP agonist, lata- noprost, induced a rapid decline in IOP within 15 min (Avila et al., 2001, 2003); however, subsequent studies by Aihara * Corresponding author at: Storm Eye Institute, 167 Ashley Avenue, Medical University of South Carolina, Charleston, SC 29425, USA. Tel.: þ1 843 792 2792; fax: þ1 843 792 1723. E-mail address: crossonc@musc.edu (C.E. Crosson). 0014-4835/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.exer.2006.08.004 Experimental Eye Research 83 (2006) 1453e1458 www.elsevier.com/locate/yexer