Age-related cataract (ARC) is one of the most common chronic diseases. Circular RNA (circ)_HIPK3 is reported to be involved in the advancement of ARC, but its molecular mechanism has not been clarified. Our study provides a new perspective on the clinical treatment of ARC. Our data showed that the expression levels of circ_HIPK3 and histone deacetylase 4 (HDAC4) were downregulated, while microRNA (miR)-495-3p level was increased in ARC tissues and H₂O₂-induced SRA01/04 cells. Functional experiments showed that circ_HIPK3 and HDAC4 overexpression could inhibit H₂O₂-induced lens epithelial cell apoptosis and fibrosis. In terms of mechanism, we found that circ_HIPK3 could sponge miR-495-3p, miR-495-3p could target HDAC4. Besides, we confirmed that circ_HIPK3 sponged miR-495-3p to positively regulate HDAC4. Additionally, miR-495-3p overexpression or HDAC4 knockdown reversed the inhibition effect of circ_HIPK3 on H₂O₂-induced lens epithelial cell injury. In conclusion, our data showed that circ_HIPK3 suppressed H₂O₂-induced lens epithelial cell injury by regulating miR-495-3p/HDAC4 axis.

年龄相关性白内障（ARC）是最常见的慢性疾病之一。据报道，环状 RNA (circ)_HIPK3 参与 ARC 的进展，但其分子机制尚未阐明。我们的研究为 ARC 的临床治疗提供了新的视角。_{我们的数据显示，在 ARC 组织和 H 2} O ₂诱导的 SRA01/04 细胞中，circ_HIPK3 和组蛋白脱乙酰酶 4 (HDAC4) 的表达水平下调，而 microRNA (miR)-495-3p 水平增加。功能实验表明circ_HIPK3和HDAC4过表达可以抑制H ₂ O ₂-诱导晶状体上皮细胞凋亡和纤维化。在机制方面，我们发现circ_HIPK3可以海绵miR-495-3p，miR-495-3p可以靶向HDAC4。此外，我们确认 circ_HIPK3 海绵化 miR-495-3p 以正向调节 HDAC4。此外，miR-495-3p 过表达或 HDAC4 敲低逆转了 circ_HIPK3 对 H ₂ O ₂诱导的晶状体上皮细胞损伤的抑制作用。总之，我们的数据表明，circ_HIPK3 通过调节 miR-495-3p/HDAC4 轴来抑制 H ₂ O ₂诱导的晶状体上皮细胞损伤。