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Gavin Roddy, Michael P Fautsch; Stanniocalcin-1, a downsteam effector molecule in latanoprost signaling, does not signal through the FP receptor for IOP reduction. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3783.
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We recently identified Stanniocalcin-1 (STC-1) as a downstream effector molecule in latanoprost signaling that was both necessary and sufficient for IOP reduction. However, it was unknown whether STC-1 and latanoprost had equivalent IOP reduction, whether the two agents were additive for IOP reduction, and if they signaled through the same cellular receptor. In the current study, we compared IOP reduction with STC-1, latanoprost, and the combination of the two agents. We additionally tested whether STC-1 signaled through the cellular receptor of latanoprost, the Prostaglandin F (FP receptor), by pharmacologically blocking the FP receptor.
C57B6J mice were treated for 5 days with daily topical application of 5 µL of one of the following treatment regimens: latanoprost-free acid (LFA; 100 µM dissolved in 1:1000 DMSO in PBS) alone, STC-1 (0.5mg/ml; Biovender Research and Diagnostic Products (Czech Republic) alone, FP receptor inhibitor AL-8810 (10mM) alone, LFA + STC-1, LFA + AL-8810, or STC-1 + AL-8810. In all cases, the contralateral eye was treated with vehicle. IOP was accessed using a handheld rebound tonometer in conscious mice during the treatment period which included 3 days of pre-treatment baseline IOP and a 3-day washout period. For purposes of statistical analysis, IOP at the treatment nadir (day 4) was used.
IOP was significantly reduced compared to vehicle control in LFA (n=6; 20.1%, P = 0.002), STC-1 (n=6, 18.7%, P<0.00001), LFA + STC-1 (n=6, 17.6%, P=0.002) treated animals. There was no significant difference when comparing treatment groups to one another. Compared to vehicle control, there was no significant difference in IOP in animals treated with AL-8810 alone or with AL-8810 + LFA. However, animals treated with AL-8810 + STC-1 demonstrated a significant IOP reduction (n=6, 22.7%, P=0.005).
STC-1 may be a novel therapy with equivalent IOP reduction as LFA that does not require signaling through the FP receptor. This may have important implications for patients that are unresponsive to latanoprost therapy
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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