Stanniocalcin-1 Is an Ocular Hypotensive Agent and a Downstream Effector Molecule That Is Necessary for the Intraocular Pressure-Lowering Effects of Latanoprost.

Autor:	Roddy GW; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Viker KB; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Winkler NS; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Bahler CK; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Holman BH; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Sheikh-Hamad D; Department of Medicine, Division of Nephrology, Baylor College of Medicine, Houston, Texas, United States., Roy Chowdhury U; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Stamer WD; Department of Ophthalmology, Duke University, Durham, North Carolina, United States., Fautsch MP; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States.
Jazyk:	angličtina
Zdroj:	Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2017 May 01; Vol. 58 (5), pp. 2715-2724.
DOI:	10.1167/iovs.16-21004
Abstrakt:	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 μL/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.
Databáze:	MEDLINE
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