Curcumin protects the diabetic mouse retina by modulating the Hippo-YAP signaling pathway

To explore the protective effects and underlying mechanisms of curcumin in preventing and treating diabetic retinopathy in the C57BL/6J diabetic mouse model.

The C57BL/6J diabetic mouse models were established through streptozotocin (STZ) induction and randomly assigned into five groups: Control, Model, Cal (0.15 g/kg•d), Cur-H (0.2 g/kg•d), and Cur-L (0.05 g/kg•d; n=10/group). Treatment was administered by oral gavage for 12wk. Upon completion of the observation period, retinal function was evaluated by electroretinography (ERG), retinal thickness and structural changes were assessed via optical coherence tomography (OCT), retinal vascular density and leakage were analyzed using optical coherence tomography angiography (OCTA) and fundus fluorescein angiography (FFA), the number of acellular capillaries in retinal flat mounts was counted, histopathological changes were observed with hematoxylin and eosin (HE) staining, and protein expression levels of components involved in the Hippo signaling pathway-Yes-associated protein (Hippo-YAP) signaling pathway and endothelial-to-mesenchymal transition (EndMT) were quantified by Western blot.

In diabetic mice, ERG amplitudes were significantly reduced, retinal thinning was observed, and the number of non-perfusion areas and acellular capillaries increased. Additionally, the phospho-large tumor suppressor kinase 1 (p-LATS1)/2/LATS1/2 and p-YAP/YAP ratios were diminished, vascular endothelial (VE)-cadherin expression was reduced, and α-smooth muscle actin (α-SMA) expression was elevated (all P<0.05). In the high-dose curcumin group, ERG amplitudes were significantly improved, retinal structure was restored, vascular density was increased, and acellular capillaries were reduced. Furthermore, the p-LATS1/2/LATS1/2 and p-YAP/YAP ratios were normalized, VE-cadherin expression was upregulated, and α-SMA expression was suppressed (all P<0.05).

Curcumin offers protective effects on the retinas of diabetic mice, likely through the modulation of the Hippo-YAP signaling pathway and the inhibition of EndMT. These findings provide support for the use of curcumin as a promising adjunctive therapy for diabetic retinopathy.