Purpose: Excessive accumulation of extracellular matrix (ECM) in the trabecular meshwork (TM) reduces aqueous humor outflow, which likely contributes to elevation of IOP in primary open-angle glaucoma (POAG). Salidroside, a phenolic glycoside isolated from Rhodiola rosea is reported to prevent profibrotic responses by inhibiting Smad signaling pathway activated by TGF-β in liver, lung, and kidney tissues. We tested if salidroside can (1) inhibit TGF-β2-induced ECM expression in cultured human TM cells, and (2) lower TGF-β2-induced ocular hypertension in the mouse.
Methods: Cultured human TM cells stimulated with 5 ng/mL TGF-β2 for 48 hours were treated with salidroside for 24 hours. The expressions of fibronectin (FN), collagen type IV (COL-IV), and 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 TGF-β2 (Ad.hTGF-β2226/228) 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.
Results: In cultured human TM cells, treatment with TGF-β2 increased expressions of FN, COL-IV, and LN, as assessed by quantitative PCR, Western blotting, 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.hTGF-β2226/228 injection) or at day 14, significantly lowered TGF-β2-induced ocular hypertension in the mouse. In contrast, salidroside did not affect IOP of control eyes.
Conclusions: These results demonstrated that salidroside is capable of minimizing TGF-β2-induced ECM expression in cultured human TM cells. It also reduced TGF-β2-induced ocular hypertension in the mouse. These findings indicate that this phenolic glycoside may be useful as a novel treatment for POAG.