Abstract
Latanoprost is a common glaucoma medication. Here, we study longitudinal effects of sustained latanoprost treatment on intraocular pressure (IOP) in C57BL/6J mice, as well as two potential side-effects, changes in iris pigmentation and central corneal thickness (CCT). Male C57BL/6J mice were treated daily for 16 weeks with latanoprost. Control mice were treated on the same schedule with the preservative used with latanoprost, benzalkonium chloride (BAK), or handled, without ocular treatments. IOP and CCT were studied at pre-treatment, 2 “early” time points, and 2 “late” time points; slit-lamp analysis performed at a late time point; and expression of corneal and iridial candidate genes analyzed at the end of the experiment. Latanoprost lowered IOP short, but not long-term. Sustained application of BAK consistently resulted in significant corneal thinning, whereas sustained treatment with latanoprost resulted in smaller and less consistent changes. Neither treatment affected iris pigmentation, corneal matrix metalloprotease expression or iridial pigment-related genes expression. In summary, latanoprost initially lowered IOP in C57BL/6J mice, but became less effective with sustained treatment, likely due to physiological adaptation. These results identify a new resource for studying changes in responsiveness associated with long-term treatment with latanoprost and highlight detrimental effects of commonly used preservative BAK.
Highlights
It is estimated that by 2020, 76 million people worldwide will be afflicted with glaucoma[1]
In order to study the effects of daily latanoprost application on mouse eyes, we obtained a cohort of C57BL/6J mice from a commercial source, randomly assigned individual mice to 1 of 3 groups (Lat, benzalkonium chloride (BAK), or Naïve) and, after 2 weeks of acclimatization to our facility, initiated our protocol
The current study shows that in C57BL/6 J mice, latanoprost is an efficient intraocular pressure (IOP)-lowering drug for short-term, but not sustained, treatment
Summary
It is estimated that by 2020, 76 million people worldwide will be afflicted with glaucoma[1]. Latanoprost is currently the most prescribed PG analog, and the recommended dosage is one drop in the affected eye, once daily in the evening[3]. It has a favorable safety/efficacy profile[2,4], it has some shortcomings. We characterize the longitudinal effects of short- and long-term latanoprost treatment on IOP in the C57BL/6J mouse strain, using a protocol that mimics the treatment regimen for glaucoma patients (once daily administration for a long period of time). At the conclusion of the longitudinal study, we performed a gene expression analysis of the cornea and iris, focusing on candidate genes that are likely to be influenced by latanoprost
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