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Lisa J. Hill, Ben Mead, Richard J. Blanch, Shabbir Mohamed, Martin Berry, Wendy Leadbeater, Ann Logan; Intercameral Decorin Attenuates Chronically Raised IOP in a Novel Rodent Model of POAG. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5088.
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© ARVO (1962-2015); The Authors (2016-present)
A major risk factor for the development of Primary Open Angle Glaucoma (POAG) is chronically raised intraocular pressure (IOP). Elevated IOP is induced by reduced outflow of aqueous humour (AH) secondary to fibrosis around Schlemm’s canal (SC) and is responsible for retinal ganglion cell (RGC) death and blindness. In this study we aimed to: 1) create a rodent model of increased IOP; 2) use this model to evaluate the IOP lowering and anti-fibrotic activity of Decorin; and 3) correlate these findings with RGC survival to establish potential neuroprotective therapies.
Male Sprague Dawley rats received bi-weekly intercameral injections of reagents (3.5µl) in 4 Groups: Group 1 (n=8) - PBS (controls) from 0-31d; Group 2 (n=8) - TGF-β (5µg/ml) from 0-31d to induce fibrosis and raise IOP; Group 3 - TGF-β (5µg/ml) from 0-17d, switched to Decorin from 17-31d to test for Decorin induced fibrolysis (n=6); and Group 4 - TGF-β (5µg/ml) from 0-31d supplemented with Decorin (5mg/ml) from 17-31d to test for blockade of fibrogenesis (n=6). IOP was measured bi-weekly and retinae processed at 31d with antibodies to laminin to assess levels of SC fibrosis by pixel counts. RGC survival was quantified using Fluorogold back-labelling.
TGF-β injections significantly increased SC fibrosis and IOP at 31d compared to PBS controls. At 31d, fibrosis and the mean IOP in Group 2 was significantly (p<0.05) higher (IOP at 17±2 mmHg) compared to Group 1 (IOP at 11±1 mmHg) (Figure1) which correlated to 27% loss of RGC (P<0.01) (Figure 2). Decorin injections combined with TGF-β prevented both SC fibrogenesis and reduced established SC fibrosis (p<0.05) (Figure 3), together with attenuating the IOP rise. Hence, Groups 3 and 4 had significantly (p<0.05) lower mean IOP to 10±0.3mmHg and 9±0.2mmHg respectively compared with Group 1.
Injections of TGF-β caused fibrosis around SC, sustained 45% increase in IOP and a 27% increase in RGC death over 31d, providing a translational model of chronic POAG. Intercameral Decorin in this model reversed nascent and established SC fibrosis and decreased IOP, demonstrating that Decorin may be an effective treatment to prevent and reverse fibrosis of SC, lower IOP and hence prevent RGC death thereby preserving visual function in patients with POAG.
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