Abstract:AIM:To investigate the regulatory effects of proanthocyanidins on autophagy and apoptosis in the retinas of guinea pigs with form-deprivation myopia via the AMPK/Wnt/β-catenin pathway.
METHODS:Fifty guinea pigs were randomly divided into a normal control group, a myopia model group, and low-dose, medium-dose, and high-dose proanthocyanidins groups(25, 50 and 100 mg/kg). Refractive power and axial length of right eye were measured using a retinoscope and A-scan ultrasound. Retinal pathological changes were observed via HE staining. Immunohistochemistry assessed p-AMPK and p-mTOR expression in the retina. Immunofluorescence detected p62 and LC3 expression. TUNEL staining evaluated retinal cell apoptosis. Western blot examined expression of proteins related to the AMPK/Wnt/β-catenin pathway and autophagy(p62, Beclin1, LC3-II/LC3-I), and apoptosis-related proteins(Bax, Bcl-2, Cleaved-Caspase3, Caspase3)in the retina.
RESULTS:Compared with the control group, the myopia model group showed significantly reduced refractive power and significantly increased axial length(both P<0.05); retinal cell arrangement became sparse and retinal thickness thinned. The p-AMPK levels in the retina were significantly reduced, while p-mTOR levels were significantly increased(both P<0.05), indicating suppression of the AMPK-Wnt/β-catenin pathway. The p62 levels were significantly elevated and LC3 levels were significantly reduced(both P<0.05), suggesting inhibition of autophagy. Bax and Cleaved-Caspase3 were significantly increased, while Bcl-2 was significantly decreased, indicating significantly increased apoptosis(both P<0.05). Compared with the myopia model group, all proanthocyanidins dose groups significantly inhibited refractive error reduction and axial length growth(both P<0.05), restored retinal cell alignment and thickness, activated the AMPK/Wnt/β-catenin pathway, significantly increased p-AMPK expression, and suppressed p-mTOR expression(all P<0.05); significantly suppressed p62 expression, increased Beclin1 and LC3-II/LC3-I expression(both P<0.05), and activated retinal autophagy; significantly suppressed Bax and Cleaved-Caspase3 expression, increased Bcl-2 expression(both P<0.05), and inhibited retinal cell apoptosis.
CONCLUSION:Proanthocyanidins enhance retinal autophagy by activating the AMPK/Wnt/β-catenin pathway, thereby inhibiting retinal apoptosis and preventing or alleviating the onset of myopia.
