Abstract
Prostaglandin F2 alpha (PGF2α) analogues such as latanoprost are common first-line intraocular pressure (IOP) lowering medications. However, their clinical use is limited in some patient populations due to minimal or no IOP lowering response or side effects. In searching for a more targeted approach for IOP reduction, our lab recently identified Stanniocalcin-1 (STC-1) as a molecule that was required for latanoprost-mediated IOP reduction and also acted as a stand-alone IOP lowering agent. In order to determine whether latanoprost and STC-1 were equivalent and/or additive for IOP reduction, we treated C57BL/6J mice with one or a combination of these agents and measured IOP. Importance of the FP receptor for latanoprost- and STC-1-mediated IOP reduction was examined in C57BL/6J mice utilizing the pharmacologic FP receptor inhibitor AL-8810 as well as FP receptor knockout mice generated in our laboratory. Latanoprost-free acid (LFA) and STC-1 reduced IOP to a similar degree and were non-additive in C57BL/6J mice. As expected, the IOP lowering effects of LFA were abrogated by pharmacologic inhibition of the FP receptor with AL-8810 and in FP receptor knockout mice. In contrast, STC-1 maintained IOP-lowering effects in the presence of AL-8810 and also in FP receptor knockout mice. These results suggest that LFA and STC-1 show equivalent and non-additive IOP reduction in C57BL/6J mice and that unlike LFA, STC-1-mediated IOP reduction occurs independent of the FP receptor.
Highlights
Glaucoma is the leading cause of irreversible visual impairment, estimated to afflict up to 80 million people worldwide [1, 2]
In order to compare STC-1 and Latanoprost-free acid (LFA) and determine whether the intraocular pressure (IOP) lowering effects were additive, C57BL/6J wild-type mice were treated with either LFA, STC-1, or a combination of LFA and STC-1 given sequentially at the same concentration and amount as when applied alone
At treatment days 4 and 5, STC-1 (12.7 ± 1.0 vs 15.3 ± 0.9 mmHg, 17% reduction, P
Summary
Glaucoma is the leading cause of irreversible visual impairment, estimated to afflict up to 80 million people worldwide [1, 2]. All available treatments for glaucoma are directed at reducing elevated intraocular pressure (IOP), the most prevalent and only treatable risk factor for glaucoma. Eye drop therapy is initially used for IOP reduction, and of the available medications, prostaglandin F2 (PGF2α) analogues are often used as first-line IOP reducing therapy for patients with glaucoma and ocular hypertension [3]. Stanniocalcin-1 reduces intraocular pressure independent of the FP receptor
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