Identification and characterization of extrachromosomal circular DNA in patients with high myopia and cataract

ABSTRACT

To explore the presence of extrachromosomal circular DNA (eccDNA) in the anterior capsule of the lens in the eyes of patients with cataract and with high myopia. Circle-Seq was performed to identify differences in the eccDNA and gene expression between the anterior capsule of the lens of patients with simple nuclear cataract (C, n = 6 cases) and patients with nuclear cataract along with high myopia (HM, n = 6 cases). The expression of eccDNA was confirmed using routine quantitative polymerase chain reaction. The eccDNA ranked in C and HM ranged in length from 0.017 kb − 9.9 Mb with two distinctive peaks detected at 0.2 kb and 0.5 kb, while eccDNA that were differentially expressed ranged in size from 0.05 kb − 57.8 kb with two distinctive peaks observed at 0.1 kb and 0.5 kb. Only 2.5% of the eccDNA in C and 2% in HM were>25 kb in size. The gene-rich chromosomes contributed to more number of eccDNA/Mb, while several well-known high myopia candidate genes, including catenin delta 2 (CTNND2) and ubiquitin-like with PHD, exhibited significantly increased levels of eccDNA in the anterior capsule of the lens in patients with high myopia. This study highlighted the topologic analysis of the anterior capsule of eyes with high myopia, which is an emerging direction for research and clinical applications. These findings suggested that eccDNA was commonly detected in eyes with high myopia and cataracts, and the candidate genes for high myopia identified in previous studies were also observed in the eccDNA.

KEYWORDS:

• Extrachromosomal circular DNA
• high myopia
• cataract
• Circle-seq
• anterior capsule of the lens

Acknowledgments

The author thanks NewCore BiodataStudio in Shanghai for sequencing date analysis; Jing Sun and Yang Cai for important clinical and scientific suggestions. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript. Each author listed on the manuscript has seen and approved the submission of this version of the manuscript and takes full responsibility for the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

GEO Series accession number GSE207646 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE207646)

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15592294.2023.2192324

Additional information

Funding

This work was supported by the [Autonomous and open project of Tianjin Key Laboratory of Retinal Function and Diseases] under Grant[number 2020tjswmm002]; [Funded by Tianjin Key Medical Discipline (Specialty) Construction Project] under Grant [number TJYXZDXK-037A]; [Tianjin Education Commission Scientific Research Project (Natural Science)] under Grant [number 2022ZD059]; [Tianjin Science and Technology Plan Project (subject)] under Grant [number 21KPHDRC00140];[The Science&Technology Development Fund of Tianjin Education Commission for Higher Education] under Grant [number 2020KJ179];[Talent program of Tianjin medical university eye hospital] under Grant [number YDYYRCXM-B2018-01LC].