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The role of corneal endothelium in macular corneal dystrophy development and recurrence

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Abstract

Macular corneal dystrophy (MCD) is a progressive, bilateral stromal dystrophic disease that arises from mutations in carbohydrate sulfotransferase 6 (CHST6). Corneal transplantation is the ultimate therapeutic solution for MCD patients. Unfortunately, postoperative recurrence remains a significant challenge. We conducted a retrospective review of a clinical cohort comprising 102 MCD patients with 124 eyes that underwent either penetrating keratoplasty (PKP) or deep anterior lamellar keratoplasty (DALK). Our results revealed that the recurrence rate was nearly three times higher in the DALK group (39.13%, 9/23 eyes) compared with the PKP group (10.89%, 11/101 eyes), suggesting that surgical replacement of the corneal endothelium for treating MCD is advisable to prevent postoperative recurrence. Our experimental data confirmed the robust mRNA and protein expression of CHST6 in human corneal endothelium and the rodent homolog CHST5 in mouse endothelium. Selective knockdown of wild-type Chst5 in mouse corneal endothelium (ACsiChst5), but not in the corneal stroma, induced experimental MCD with similar extracellular matrix synthesis impairments and corneal thinning as observed in MCD patients. Mice carrying Chst5 point mutation also recapitulated clinical phenotypes of MCD, along with corneal endothelial abnormalities. Intracameral injection of wild-type Chst5 rescued the corneal impairments in ACsiChst5 mice and retarded the disease progression in Chst5 mutant mice. Overall, our study provides new mechanistic insights and therapeutic approaches for MCD treatment by high-lighting the role of corneal endothelium in MCD development.

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Data availability

Original data created for the study will be available upon publication. Mouse transcriptome data have been deposited in the Genome Sequence Archive (GSA, https://ngdc.cncb.ac.cn/gsa/) with the accession number CRA005419. The human microarray data has been deposited in the OMIX Database (https://ngdc.cncb.ac.cn/omix/) under the accession number OMIX730.

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Acknowledgements

This work was supported by the Shandong Provincial Natural Science Foundation (ZR2020QH140), the National Natural Science Foundation of China (82101091), the Academic Promotion Program of Shandong First Medical University (2019ZL001, 2019RC008), the Shandong Provincial Key Research and Development Program (2021ZDSYS14). The authors would like to thank Dr. Can Zhao for refining the microinjection method, Ting Liu for providing corneal paraffin sections from MCD patients, Rui Cao and Li Gao for providing human corneal tissues, Xia Qi and Guoying Liu for refining alcian blue staining protocol.

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Authors and Affiliations

  1. Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, China

    Bi-Ning Zhang, Benxiang Qi, Chunxiao Dong, Bin Zhang, Jun Cheng, Xiaoyun Zhuang, Shijiu Chen, Haoyun Duan, Dewei Li, Qingjun Zhou & Lixin Xie

  2. State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Qingdao, 266071, China

    Bi-Ning Zhang, Benxiang Qi, Bin Zhang, Jun Cheng, Xin Wang, Suxia Li, Haoyun Duan, Dewei Li, Qingjun Zhou & Lixin Xie

  3. School of Ophthalmology, Shandong First Medical University, Qingdao, 250021, China

    Bi-Ning Zhang, Benxiang Qi, Chunxiao Dong, Bin Zhang, Jun Cheng, Xin Wang, Suxia Li, Xiaoyun Zhuang, Shijiu Chen, Haoyun Duan, Dewei Li, Qingjun Zhou & Lixin Xie

  4. Department of Medicine, Qingdao University, Qingdao, 266071, China

    Chunxiao Dong & Shijiu Chen

  5. Eye Institute of Shandong First Medical University, Eye Hospital of Shandong First Medical University (Shandong Eye Hospital), Jinan, 250021, China

    Xin Wang & Suxia Li

  6. Department of Ophthalmology, School of Clinical Medicine, Weifang Medical University, Weifang, 261072, China

    Xiaoyun Zhuang

  7. Institute of Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266071, China

    Sujie Zhu

  8. Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266071, China

    Guoyun Li

  9. Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266071, China

    Guoyun Li

  10. Department of Microbiology, Tumor and Cell Biology, Biomedicum, Karolinska Institutet, Stockholm, 17177, Sweden

    Yihai Cao

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  1. Bi-Ning Zhang
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  2. Benxiang Qi
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  3. Chunxiao Dong
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  4. Bin Zhang
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  6. Xin Wang
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  7. Suxia Li
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  8. Xiaoyun Zhuang
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  9. Shijiu Chen
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  10. Haoyun Duan
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  11. Dewei Li
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  13. Guoyun Li
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  14. Yihai Cao
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  15. Qingjun Zhou
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  16. Lixin Xie
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Corresponding authors

Correspondence to Qingjun Zhou or Lixin Xie.

Ethics declarations

The authors declare no competing interest. This study was conducted in compliance with the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of Qingdao Eye Hospital (2021-09). Informed consent was obtained from the participants involved in the study. The use of data in this was approved by the Academic Board of Qingdao Eye Institute. Corneal tissues from healthy donors were obtained from the Eye Bank of Qingdao Eye Hospital, while diseased corneas from MCD patients were collected during corneal transplantation surgeries. The animal study protocols were approved by the Animal Investigation Committee of the Eye Institute of Shandong First Medical University. All animal procedures were performed in accordance with The Association for Research in Vision and Ophthalmology (ARVO) statement.

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Zhang, BN., Qi, B., Dong, C. et al. The role of corneal endothelium in macular corneal dystrophy development and recurrence. Sci. China Life Sci. 67, 332–344 (2024). https://doi.org/10.1007/s11427-023-2364-3

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  • DOI: https://doi.org/10.1007/s11427-023-2364-3

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