TY - JOUR
T1 - Effects of sustained daily latanoprost application on anterior chamber anatomy and physiology in mice
AU - Dutca, Laura M.
AU - Rudd, Danielle
AU - Robles, Victor
AU - Galor, Anat
AU - Garvin, Mona K.
AU - Anderson, Michael G.
N1 - Funding Information:
We would like to thank Carly Lewis and Hannah Mercer for helping with the long-term treatments, Drs. Demelza Koehn and Kacie Meyer for assistance in designing some of the primers, and Dr. Johannes Ledolter for helpful discussions. This work was supported by US Dept. of Veterans Affairs, RR&D (I01RX001481), and National Institutes of Health, NEI (R01EY017673) grants to MGA. Additional support was provided by NIH/NEI Center Support Grant P30EY025580 (University of Iowa); US Dept. of Veterans Affairs, RR&D IK2 RX002003 (Dr. Dutca); US Dept. of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research EPID-006-15S (Dr. Galor); R01EY026174 (Dr. Galor); NIH Center Core Grant P30EY014801 (University of Miami); and Research to Prevent Blindness Unrestricted Grant (University of Miami). The contents do not represent the views of the U.S. Department of Veterans Affairs or the U.S. Government.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-018-31280-1
DO - 10.1038/s41598-018-31280-1
M3 - Article
C2 - 30166564
AN - SCOPUS:85052698112
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 13088
ER -