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Purpose/Aim : Glaucomatous optic neuropathy (GON) remains the world's leading cause of irreversible blindness. Treatments including topical medications are directed at reducing intraocular pressure (IOP), the most significant risk factor for GON. Current medications, while generally effective, are limited by insufficient response and side-effects in some patients. In search of a more targeted therapy that acts downstream of existing medications that has a potential for a lower side effect profile, our laboratory has identified Stanniocalcin-1 (STC-1), a multifunctional hormone, as an effector molecule in latanoprost-mediated IOP reduction with similar IOP-lowering efficacy as latanoprost in normotensive mice. Materials and methods : To investigate whether STC-1 can also reduce IOP in ocular hypertensive mice, we used a steroid-induced ocular hypertensive mouse model characterized by trabecular meshwork dysfunction as well as the DBA/2J mouse as an inherited model of pigment dispersion and secondary angle closure. Steroid-induced ocular hypertension was induced by weekly injections of dexamethasone into the conjunctival fornix of wild-type C57BL/6J mice (6-8 months old). After confirmation of the steroid response, mice were administered STC-1 or phosphate buffered saline (PBS) topically once daily for six weeks. For DBA/2J mice (14 months old), after baseline IOP measurements, mice were treated topically once daily with STC-1 or PBS for 5 days and IOP was assessed twice daily. Results : In steroid-induced ocular hypertensive mice, STC-1 lowered IOP by 26% ( P < .001, week three) and maintained this level of IOP reduction throughout the remainder of the treatment period ( P < .001, week six). In DBA/2J mice, STC-1 lowered IOP by 37% ( P < .001). Conclusions : Together, these data show that STC-1 reduced IOP in two models of ocular hypertension with different mechanisms of outflow obstruction.

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., Competing Interests: 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

Purpose: To investigate the precision and accuracy of IOP measurements using a pneumatonometer and a tonometer tip cover (Tono-Pen ® tip cover) acting as a membrane between a cadaver eye model and pneumatonometer probe., Methods: A total of 480 paired IOP measurements, with and without a Tono-Pen cover, were collected across 4 pressure levels of 7, 10, 20 and 30 mmHg. IOP measurements were obtained by three different pneumatonometer units paired with three different masked operators (three configurations). Four eyes were sampled for each eye pressure level. The sequence of eye pressure, configuration, and measurements with vs. without the Tono-Pen cover was randomized., Results: With the Tono-Pen cover in place, there was a negative bias with a mean IOP difference of - 1.18 mmHg for all 480 paired samples compared with the measurements absent the cover. Compared with the test pressure settings (i.e., 7, 10, 20, 30 mmHg), the overall mean bias was + 0.35 mmHg with the Tono-Pen cover present. With the Tono-Pen cover present, the overall repeatability %CV (percent coefficient of variation) was 3.4% and the reproducibility %CV was 3.8% compared with a repeatability %CV of 3.2% and reproducibility %CV of 5.7% without the Tono-Pen cover., Conclusion: Measurement of IOP via pneumatonometry with a Tono-Pen cover in place, also known as the excursion test method, yields precise, accurate and reproducible results. This developed method of pressure measurement is an acceptable and reliable form of IOP measurement.