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

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.

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.

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.

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.

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.