目的：分析染色体外环状DNA（extrachromosomal circular DNA, eccDNA）的分子特征及潜在功能，初步探索eccDNA在合并人类免疫缺陷病毒（human immunodeficiency virus, HIV）感染患者的白内障发病过程中的作用机制。方法：收集4例合并HIV感染的并发性白内障（complicated cataract, CC）患者及性别、年龄与之匹配的4例年龄相关性白内障（age-related cataract, ARC）患者晶状体囊膜，通过提取、滚环扩增及circle-seq对eccDNA进行全长测序，分析比较合并HIV感染的CC患者及ARC患者之间晶状体囊膜eccDNA的数量、长度分布、基因组元件分布及eccDNA相关差异基因功能富集情况。结果：合并HIV感染的CC患者晶状体囊膜中eccDNA数量较ARC患者增多，鸟嘌呤（guanine, G）和胞嘧啶（cytosine，C）碱基所占的比例（GC含量）较ARC患者减少。在CC患者及ARC患者中，eccDNA的长度在1 200 ~1 800 bp均分布最多，CC患者在2 000~2 200 bp之间呈现另一部分高峰，ARC组则在此区间eccDNA丰度极低。CC患者eccDNA来源基因组元件在CpG岛占比低于ARC组。 CC患者组eccDNA差异基因富集的通路多与钙信号通路、Apelin信号通路及cGMP-PKG信号通路相关。结论：合并HIV感染的CC患者与ARC患者晶状体囊膜eccDNA的分子特征存在差异，提示eccDNA可能通过基因表达调控晶状体前囊膜代谢功能影响CC的发生、发展。

Objective: To perform full-length sequencing of extrachromosomal circular DNA (eccDNA) in the lens capsule of patients with human immunodeficiency virus (HIV)-infected complicated cataract (CC) and age-related cataract (ARC). The aim is to analyze the molecular characteristics and potential functions of eccDNA and initially investigate the mechanism by which eccDNA contributes to the pathogenesis of cataract related to HIV infection. Methods: Lens capsules were collected from 4 CC patients who were co-infected with HIV and from ARC patients matched for gender and age. The eccDNA was sequenced following a process that included extraction, rolling circle amplification, and circle-seq. We then analyzed and compared the number, length distribution, genomic element distribution, and enrichment of differential gene functions associated with eccDNA in the lens capsules of CC patients co-infected with HIV and ARC patients. Results: The number of eccDNA molecules in the lens capsule of CC patients co-infected with HIV was significantly higher than that in ARC patients, while the GC content was lower.. In both CC and ARC patients, the majority of eccDNA lengths felll within the range of 1200 to 1800 bp. However, CC patients exhibited an additional peak between 2000 and 2200 bp, where the abundance of eccDNA in the ARC group was extremely low. Regarding genomic elements derived from eccDNA, the proportion in CC patients was lower than that in the ARC group within CpG islands. The pathways associated with differential gene enrichment of eccDNA in CC patients were primarily related to the calcium signaling pathway, Apelin signaling pathway, and cGMP-PKG signaling pathway. Conclusions: There are notable differences in the molecular characteristics of lens capsule eccDNA between CC patients with HIV infection and ARC patients.These finding suggest that eccDNA may influence the onset and progression of CC by regulating the metabolic functions of the anterior lens capsule through gene expression.