From liver to lens: How low-intensity ultrasound targets diabetic cataract mechanisms.

BACKGROUND

Diabetic cataract is a common complication of diabetes, and current clinical management mainly relies on surgical intervention, with limited preventive strategies available. This study aimed to investigate whether liver-targeted low-intensity pulsed ultrasound (LIPUS) can prevent or delay the progression of diabetic cataract and to elucidate the underlying molecular mechanisms.

METHODS

A type 2 diabetes mellitus rat model was established using a high-fat diet combined with streptozotocin. Animals were divided into Normal, Model, and LIPUS groups. The LIPUS group received liver irradiation (200 mW/cm2, 10 min/day for 30 days). Lens opacity was assessed using slit-lamp examination, and blood glucose, branched-chain amino acids (BCAAs), and PRKAR1A expression were measured. In vitro experiments included co-culture of hepatocytes (AML12) and lens epithelial cells (SRA01/04) and siRNA transfection assays. Statistical analysis was performed using independent-samples t-tests and two-way ANOVA.

RESULTS

LIPUS significantly delayed the onset and progression of diabetic cataract, reduced blood glucose levels and hepatic/serum BCAAs, and restored PRKAR1A expression in lens epithelial cells. LIPUS also inhibited epithelial-mesenchymal transition (EMT) by upregulating E-cadherin and downregulating α-SMA. Knockdown of PRKAR1A reversed the inhibitory effect of LIPUS on EMT. Additionally, LIPUS improved liver and pancreatic histopathology without causing detectable tissue damage.

CONCLUSION

LIPUS prevents diabetic cataract through dual mechanisms: improving glucose homeostasis and reducing BCAAs levels to restore PRKAR1A expression, thereby inhibiting EMT in lens epithelial cells. These findings suggest that LIPUS represents a safe and non-invasive strategy for diabetic cataract prevention and highlight BCAAs and glucose metabolism as potential therapeutic targets.

ONE SENTENCE SUMMARY: This study demonstrates that targeted hepatic application of low-intensity pulsed ultrasound (LIPUS) effectively delays diabetic cataract progression in rats by suppressing lens epithelial cell EMT through dual mechanisms-directly lowering blood glucose and reducing hepatic BCAA production to restore PRKAR1A expression via the liver-lens axis-thereby offering a promising non-invasive preventive strategy that concurrently improves systemic glucose metabolism.