| First Author | Roddy GW | Year | 2017 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 58 |
| Issue | 5 | Pages | 2715-2724 |
| PubMed ID | 28538979 | Mgi Jnum | J:254649 |
| Mgi Id | MGI:6112316 | Doi | 10.1167/iovs.16-21004 |
| Citation | Roddy GW, et al. (2017) Stanniocalcin-1 Is an Ocular Hypotensive Agent and a Downstream Effector Molecule That Is Necessary for the Intraocular Pressure-Lowering Effects of Latanoprost. Invest Ophthalmol Vis Sci 58(5):2715-2724 |
| abstractText | Purpose: To identify downstream signaling molecules through which intraocular pressure (IOP) is lowered following treatment with the prostaglandin analog latanoprost. Methods: Total RNA and protein isolated from primary human Schlemm''s canal cells (n = 3) treated with latanoprost (free acid; 100 nM) were processed for quantitative PCR and Western blot analysis. IOP was evaluated in stanniocalcin-1 (STC-1-/-) and wild-type mice following treatment with latanoprost or Rho kinase inhibitor Y27632. Human anterior segment pairs (n = 8) were treated with recombinant STC-1 (5, 50, or 500 ng/mL) and pressure was recorded using custom-designed software. The effect of recombinant STC-1 (0.5 mg/mL) on IOP was evaluated in wild-type mice. Tissue morphology was evaluated by light and transmission electron microscopy. Results: Increased STC-1 mRNA (4.0- to 25.2-fold) and protein expression (1.9- to 5.1-fold) was observed within 12 hours following latanoprost treatment. Latanoprost reduced IOP in wild-type mice (22.0% +/- 1.9%), but had no effect on STC-1-/- mice (0.5% +/- 0.7%). In contrast, Y27632 reduced IOP in both wild-type (12.5% +/- 1.2%) and in STC-1-/- mice (13.1% +/- 2.8%). Human anterior segments treated with STC-1 (500 ng/mL) showed an increase in outflow facility (0.15 +/- 0.03 to 0.27 +/- 0.09 muL/min/mm Hg) while no change was observed in paired vehicle-treated controls. Recombinant STC-1 reduced IOP in wild-type mice by 15.2% +/- 3.0%. No observable morphologic changes were identified between treatment groups when evaluated by microscopy. Conclusions: Latanoprost-induced reduction of IOP is mediated through the downstream signaling molecule STC-1. When used by itself, STC-1 exhibits ocular hypotensive properties. |
