Salidroside Reverses Experimental Myopia by Restoring Collagen I Homeostasis via 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.