Stanniocalcin-1 (STC-1), a downstream effector molecule in latanoprost signaling, acts independent of the FP receptor for intraocular pressure reduction.

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.

Déclaration de conflit d'intérêts

GWR has intellectual property related to STC-I. Specific information is included below. None of these patients are related to STC-I and intraocular pressure reduction. GWR has received no royalties from any of these patents. GWR has no products in development. No other co-authors declare conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Title Patent Number Protein therapy for corneal inflammation, epithelial wound 8759298 healing, and photoreceptor degeneration Robert Rosa, Gavin W. Roddy, Darwin J. Prockop Adult stem/progenitor and stem cell proteins for treatment of 8785395 eye injuries and diseases. 1 Country Date Filed Date Issued US 07/2012 06/2014 US 10/2011 06/2014 Darwin J. Prockop, Joo Youn Oh, Gavin W. Roddy, Robert Rosa, Barry A. Berkowitz Adult stem/progenitor and stem cell proteins for treatment of eye injuries and diseases Darwin J. Prockop, Joo Youn Oh, Barry Berkowitz, Gavin W. Roddy, Robert Rosa 9062103 US 11/2014 06/2015 Adult stem/progenitor and stem cell proteins for treatment of eye injuries and diseases Darwin Prockop, Joo Youn Oh, Barry Berkowitz, Gavin Roddy, Robert Rosa 9730961 US 08/2015 08/2017