Salidroside Reverses Experimental Myopia by Restoring Collagen I Homeostasis <i>via</i> Activation of the microRNA-203a-3p/Matrix Metalloproteinase-2 Axis

PURPOSE: High myopia is a leading cause of visual impairment and blindness, characterized by axial elongation of the eyeball and changes in the sclera, particularly remodeling of extracellular matrix components. Salidroside, a natural glycoside from Rhodiola crenulata, has anti-hypoxic, anti-inflammatory, and antioxidant properties. However, its role in myopia progression remains unclear. This study aimed to explore the effects of salidroside on scleral microRNA (miR)-203a-3p, matrix metalloproteinase (MMP)-2, and collagen I in a form-deprivation myopia rat model. METHODS: Experimental myopia was induced in Sprague-Dawley rats through monocular form deprivation for four weeks. Rats were orally administered low, medium, or high doses of salidroside (10, 20, and 40 mg/kg/day) starting one week after form deprivation. The scleral levels of miR-203a-3p, MMP2, and collagen I were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. A dual-luciferase reporter assay confirmed the interaction between miR-203a-3p and the 3'-untranslated region (UTR) of MMP2. Biometric parameters, including axial length and refractive error, were assessed to evaluate the therapeutic efficacy of salidroside. RESULTS: Form deprivation led to significant changes in scleral molecular markers, including upregulation of MMP2 and downregulation of miR-203a-3p and collagen I. Salidroside treatment dose-dependently reversed these changes, restoring miR-203a-3p levels, inhibiting MMP2 expression, and promoting collagen I synthesis. The dual-luciferase assay confirmed direct targeting of MMP2 by miR-203a-3p. In biometric analyses, salidroside significantly reduced axial elongation and myopic refractive shift, demonstrating its potential to slow myopia progression. Co-treatment with a miR-203a-3p mimic and salidroside enhanced these effects, suggesting a synergistic relationship between miR-203a-3p and salidroside. CONCLUSIONS: Salidroside exerts protective effects against high myopia progression by regulating the miR-203a-3p/MMP2 axis and enhancing collagen I synthesis. These findings position salidroside as a promising pharmacological candidate for myopia treatment, offering a novel therapeutic approach to mitigate structural changes associated with myopia progression.