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Dose-dependent therapeutic effects of topical 1,25 OH-vitamin D3 on corneal wound healing

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Abstract

Conflicting results have been reported regarding the effects of 1,25 OH-vitamin D3 on corneal wound healing. Therefore, we undertook this study to determine whether the observed differences are dose related. The dose-dependent effects of 1,25 OH-vitamin D3 on corneal wound healing were evaluated using scratch assays on human corneal limbal-epithelial cells (HCLEs) and in vivo mouse corneal epithelial debridement. To evaluate the anti-inflammatory effects of 1,25 OH-vitamin D3, macrophages were stimulated by a Toll-Like Receptor (TLR) ligand followed by treatment with the 10−6 M, 10−7 M and 10−8 M 1,25 OH-vitamin D3. 10−7 M 1,25 OH-vitamin D3 induced faster scratch wound closure compared with the other concentrations of 1,25 OH-vitamin D3 tested (10–6 M and 10–8 M), and 0.02% ethanol as a control (85.8 ± 2.6%, 33.9 ± 6.74%, 32.6 ± 3.35%, and 31.6 ± 3.99%, respectively, P < 0.0001). Single-time treatment with 10–7 M 1,25 OH-vitamin D3 also significantly improved the healing of mouse corneal epithelial wound compared to multiple treatments and control (74.1 ± 17.3% vs. 52.4 ± 11.6% and 45.8 ± 13.4%, respectively). Polyinosinic: polycytidylic acid (poly [I:C])-stimulated macrophage cells and 10−7 M 1,25 OH-vitamin D3 significantly decreased gene expression of ICAM1, TLR3, IL6, IL8, and TNFα (P < 0.0001). Our results suggest the dose-dependent therapeutic effect of 1,25 OH-vitamin D3 in corneal wound healing which can be potentially used as a non-invasive option in the treatment of corneal wounds.

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Acknowledgements

This work was supported by R01 EY024349 (ARD), K12 EY021475(KBK); unrestricted grant to the department from Research to Prevent Blindness, and Eversight (providing both seed funding and human corneal research tissue). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Ophthalmology and Visual Sciences, University of Illinois At Chicago, 1905 W. Taylor St. L-213, Chicago, 60612, USA

    Sayena Jabbehdari, Ghasem Yazdanpanah, Eric Chen, Neda Afsharkhamseh, Mahmood Ghassemi, Khandaker N. Anwar, Cheryl Fonteh, Ali R. Djalilian & Kai B. Kang

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  1. Sayena Jabbehdari
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  2. Ghasem Yazdanpanah
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Contributions

S.J., K.K.: conceptualization, final approval of manuscript; S.J, G.Y., E.C., N.A.: manuscript writing, collection and/or assembly of data, data analysis, data interpretation; S.J., G.Y., M.G., K.K., C.F., A.R.D.: writing—review and editing; A.R.D.: funding acquisition.

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Correspondence to Kai B. Kang.

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Jabbehdari, S., Yazdanpanah, G., Chen, E. et al. Dose-dependent therapeutic effects of topical 1,25 OH-vitamin D3 on corneal wound healing. Mol Biol Rep 48, 4083–4091 (2021). https://doi.org/10.1007/s11033-021-06418-6

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