Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang, China.
Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang, China; Eye Department, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, China.
Arch Biochem Biophys. 2024 Nov;761:110180. doi: 10.1016/j.abb.2024.110180. Epub 2024 Oct 11.
ARC (Age-related cataract) is one of the leading causes of vision impairment and blindness; however, its pathogenesis remains unclear. FYCO1 (FYVE and coiled-coil domain containing 1) serves as an autophagy adaptor. The present study investigated the role of FYCO1 in cataract.
Ultraviolet-B (UVB) irradiation was used to establish a cataract mice model. Hematoxylin and eosin (H&E) assay were used to observe lens morphology. Cell models were constructed by cultivating SRA 01/04 cells with HO and UVB. Cell counting kit-8 (CCK8) and Senescence-associated β-galactosidase (SA-β-Gal) assay were performed to explore proliferation and senescence. The gene and protein expression were assessed by quantitative real-time PCR (qRT-PCR), Western blot and immunofluorescence staining.
We demonstrated lens structural damage and downregulation of FYCO1 in mice with UVB-induced cataracts. In vitro results revealed a deletion in autophagy levels along with the decrease of FYCO1 expression in human lens epithelial cells (HLECs) after HO treatment, which was confirmed in vivo. The knockout of FYCO1 in the HLECs did not change basal autophagy and senescence but suppressed HLECs response in the induction of both. Further investigation indicated that FYCO1 knockout inhibited senescence and p21 levels by suppressing the expression of p21 activated kinase 1 (PAK1) in cataract cell models.
This study has newly characterized the role of FYCO1 in UVB-induced cataracts and in oxidative stress, both of which are associated with ARCs. A novel association between FYCO1 and PAK1/p21 in lens epithelial cell autophagy, senescence, and cataractogenesis also appears to have been established.
年龄相关性白内障（ARC）是导致视力损害和失明的主要原因之一，但发病机制尚不清楚。FYCO1（FYVE 和卷曲螺旋结构域包含 1）作为自噬衔接蛋白。本研究探讨了 FYCO1 在白内障中的作用。
采用紫外线-B（UVB）照射建立白内障小鼠模型。苏木精和伊红（H&E）染色观察晶状体形态。培养 SRA 01/04 细胞并用 HO 和 UVB 构建细胞模型。通过细胞计数试剂盒-8（CCK8）和衰老相关β-半乳糖苷酶（SA-β-Gal）检测法研究增殖和衰老情况。通过实时定量 PCR（qRT-PCR）、Western blot 和免疫荧光染色评估基因和蛋白表达。
我们发现，在 UVB 诱导的白内障小鼠中，晶状体结构受损，FYCO1 表达下调。体外结果显示，在 HO 处理后，人晶状体上皮细胞（HLECs）中自噬水平降低，FYCO1 表达下调，这在体内得到了证实。在 HLECs 中敲除 FYCO1 不会改变基础自噬和衰老，但会抑制两者诱导的 HLECs 反应。进一步研究表明，FYCO1 敲除通过抑制 p21 激活激酶 1（PAK1）的表达抑制白内障细胞模型中的衰老和 p21 水平。
本研究首次阐明了 FYCO1 在 UVB 诱导的白内障和氧化应激中的作用，这两者都与 ARC 有关。FYCO1 与 PAK1/p21 在晶状体上皮细胞自噬、衰老和白内障发生中的新关联也似乎已经建立。
