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tao guo, yuchen fan, li guo, jiahong wei; Effects of Salidroside on Trabecular Meshwork Cell Extracellular Matrix Expression and Mouse Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5154.
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© ARVO (1962-2015); The Authors (2016-present)
Excessive accumulation of extracellular matrix (ECM) in the trabecular meshwork (TM) reduces aqueous humor outflow, which likely contributes to elevation of intraocular pressure (IOP) in primary open-angle glaucoma (POAG). Salidroside, a phenolic glycoside isolated from R. rosea is reported to prevent pro-fibrotic responses by inhibiting Smad signaling pathway activated by TGFβ in liver, lung, and kidney tissues. We tested if salidroside can (1) inhibit TGFβ2-induced ECM expression in cultured human TM cells, and (2) lower TGFβ2-induced ocular hypertension in the mouse.
Cultured human TM cells stimulated with 5 ng/mL TGFβ2 for 48 h were treated with salidroside for 24 h. The expressions of fibronectin (FN), collagen type IV (COL-IV), laminin (LN) were evaluated by quantitative PCR, western blot, and immunocytochemistry. BALB/cJ mice were injected intravitreally with an adenoviral vector encoding a bioactive mutant of TGFβ2 (Ad.hTGFβ2226/228) in one eye to induce ocular hypertension, with the uninjected contralateral or Ad.Empty-injected eyes serving as controls. Mice were treated with a daily intraperitoneal injection of 40 mg/kg salidroside. Conscious mouse IOP values were measured using a TonoLab rebound tonometer.
In cultured human TM cells, treatment with TGFβ2 increased expressions of FN, COL-IV, and LN, as assessed by qPCR, western blot, and immunocytochemistry, all of which were significantly and completely ameliorated by 30 μM salidroside. Daily intraperitoneal injections of salidroside (40 mg/kg), starting either at Day 0 (same day as Ad.hTGFβ2226/228 injection) or at Day 14, significantly lowered TGFβ2-induced ocular hypertension in the mouse. In contrast, salidroside did not affect IOP of control eyes.
These results demonstrated that salidroside is capable of minimizing TGFβ2-induced ECM expression in cultured human TM cells. It also reduced TGFβ2-induced ocular hypertension in the mouse. These findings indicate that this phenolic glycoside may be useful as a novel treatment for POAG.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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