In the present study, we confirmed that TGR5 ameliorated mitochondrial homeostasis by inhibiting mitochondrial fission and enhancing mitophagy throngh the PKCδ/Drp1-HK2-PINK1/Parkin signaling pathway, thereby improving endothelial dysfunction and alleviating DR progression (Figure 7). Here, PRKN is linked to endothelial dysfunction.