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Correlation between preoperative aqueous cytokine levels and mid-term corneal endothelial cell loss following penetrating keratoplasty

Eye volume 39, pages 1286–1291 (2025)Cite this article

Subjects

Abstract

Objective

To investigate the association between preoperative aqueous humour (AqH) cytokines and mid-term endothelial cell density (ECD) following penetrating keratoplasty (PKP).

Methods

This study analysed a total of 87 eyes of which 54 underwent PKP and 33 eyes underwent cataract surgery. AqH samples were collected at the beginning of surgery. The levels of cytokines (interleukins [ILs]-1α, -1β, -4, -6, -8, -10, -17A, monocyte chemotactic protein [MCP]-1, interferon [IFN]-α, IFN-γ, E-selectin, P-selectin, and soluble intercellular adhesion molecule-1 [sICAM-1]) in the AqH were measured using a multiplex beads immunoassay. The subjects who underwent PKP were classified into two groups: Group 1: ECD < 1200 cells/mm2 at 36 months and graft failure during follow-up (38 eyes); Group 2 ECD ≥ 1200 cells/mm2 at 36 months (16 eyes).

Results

The ECD reduction per year was significantly correlated with the preoperative levels of protein (r = 0.48; P < 0.001), IL-6 (r = 0.29; P = 0.048), IL-8 (r = 0.42; P = 0.003), IL-12p70 (r = 0.46; P = .007), MCP-1 (r = 0.28; P = 0.049), IFN -γ (r = 0.43; P = 0.008), and s-ICAM-1 (r = 0.30; P = 0.03). The preoperative levels of IL-8, and IFN-γ in AqH were significantly higher in eyes with ECD < 1200 cells/mm2 compared to those with ECD ≥ 1200 cells/mm2 at 3 years (P ≤ 0.02).

Conclusion

Preoperative AqH cytokine levels are associated with mid-term ECD reduction after PKP. Pathological alterations of the AqH microenvironment may affect mid-term corneal endothelial cell survival.

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Fig. 1
Fig. 2: Comprehensive mechanism of CEnC loss after PKP.

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Data availability

The data that support the findings of this study are available on request from the corresponding author (TY). The data are not publicly available due to them containing information that could compromise research participant privacy/consent.

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Acknowledgements

We would like to thank Editage company for English language editing.

Funding

This study is supported by the Grant-in-Aid for Scientific Research 15K10906 and 23H03063 from the Ministry of Education, Culture, Sports, Science and Technology of Japan (TY) and Japan Agency for Medical Research and Development JP24ek0109590 (TY). The funding organisation had no role in the design or conduct of this research.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Hiroshi Matsumae

  2. Department of Ophthalmology, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan

    Kaon Kataoka, Yukari Yagi-Yaguchi, Kazunari Higa, Takanori Suzuki, Hirotsugu Kasamatsu, Jun Shimazaki & Takefumi Yamaguchi

Authors
  1. Hiroshi Matsumae
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  2. Kaon Kataoka
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  3. Yukari Yagi-Yaguchi
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  4. Kazunari Higa
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  6. Hirotsugu Kasamatsu
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  7. Jun Shimazaki
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  8. Takefumi Yamaguchi
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Contributions

Concept and design: TY. Acquisition of patient data: HM, YYY, KK, KH, TS, HK, TY. Critical revision of the manuscript for important intellectual content: JS. Management of this project: JS and TY. Statistical analysis was conducted by HM, and justified by TY. Obtained funding and supervision: TY.

Corresponding author

Correspondence to Takefumi Yamaguchi.

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Competing interests

All authors certify that we have no involvement with any entity or organisation with any financial interest in the subject matter or materials discussed in the manuscript. We have no competing interest regarding this study.

Ethics approval

This study was approved by the Institutional Ethics Review Board of Tokyo Dental College Ichikawa General Hospital (Institution Review Board No.: I-15-42R). All the procedures conformed to the tenets of the Declaration of Helsinki and the Japanese Guidelines for Life Science and Medical Research.

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Matsumae, H., Kataoka, K., Yagi-Yaguchi, Y. et al. Correlation between preoperative aqueous cytokine levels and mid-term corneal endothelial cell loss following penetrating keratoplasty. Eye 39, 1286–1291 (2025). https://doi.org/10.1038/s41433-025-03610-x

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