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Gavin W Roddy, Cindy K Bahler, Bradley H Holman, Michael P Fautsch; The neuroprotective protein Stanniocalcin-1 (STC-1) has ocular hypotensive properties in the human anterior segment organ culture model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):559.
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© ARVO (1962-2015); The Authors (2016-present)
Current therapies for glaucoma lower intraocular pressure but do not provide neuroprotection. STC-1 is a multi-functional protein that has recently been shown to be neuroprotective for photoreceptors and ganglion cells in vivo. In this study, we evaluated the ocular hypotensive properties of STC-1.
Paired human eyes (n=5) were obtained from the MN Lions Eye Bank. Following bisection of the eyes at the equator and removal of the iris, lens and vitreous, the anterior segments were clamped in a modified petri dish, placed at 37°C in a 5% CO2 atmosphere and perfused with Dulbecco’s Modified Eagle’s Media (DMEM) at the normal human flow rate of 2.5 μl/min. Upon stabilization of baseline IOP, one eye received an anterior chamber exchange with DMEM containing STC-1 (5, 50 or 500 ng/ml) while the fellow eye received an anterior chamber exchange with DMEM alone. Pressures were continuously monitored with a transducer connected to the second access cannula built into the dish and recorded with a custom designed computerized system. Histology was analyzed by transmission electron microscopy and evaluated by masked observation.
All anterior segments perfused with STC-1 at 500 ng/ml had increased outflow facility (0.15 ± 0.03 to 0.27 ± 0.09 µl/min/mmHg, n=5, P=0.02) compared to baseline. In contrast, paired controls treated with vehicle showed no change in outflow facility (0.20 ± 0.03 to 0.20 ± 0.02 µl/min/mmHg, n=5, P=0.76). Anterior segments perfused with STC-1 at 5 ng/ml (0.15 ± 0.04 to 0.15 ± 0.04 µl/min/mmHg, n=2) and 50 ng/ml (0.14 ± 0.05 to 0.18 ± 0.07 µl/min/mmHg, n=4) had no significant effect on outflow facility (P=0.09). Morphological analysis showed similar cell numbers in the trabecular meshwork and Schlemm’s canal. No major disruptions of the juxtacanalicular region or the basement membrane of Schlemm’s canal inner and outer wall were observed.
STC-1 increased outflow facility in the human anterior segment culture model. STC-1 appears to be a novel molecule that can both reduce IOP and provide neuroprotection.
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