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Biological effects of stored platelet-rich plasma eye-drops in corneal wound healing
  1. Yuichi Okumura1,2,
  2. Takenori Inomata1,2,3,4,
  3. Keiichi Fujimoto1,2,
  4. Kenta Fujio1,2,
  5. Jun Zhu1,
  6. Ai Yanagawa2,
  7. Hurramhon Shokirova1,
  8. Yoshitomo Saita5,6,
  9. Yohei Kobayashi5,6,
  10. Masahi Nagao5,6,7,
  11. Hirofumi Nishio5,6,
  12. Jaemyoung Sung1,2,8,
  13. Akie Midorikawa-Inomata3,
  14. Atsuko Eguchi3,
  15. Ken Nagino1,2,3,
  16. Yasutsugu Akasaki1,2,
  17. Kunihiko Hirosawa1,2,
  18. Tianxiang Huang1,2,
  19. Mizu Kuwahara1,2,
  20. Akira Murakami1,2
  1. 1Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
  2. 2Department of Digital Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
  3. 3Department of Hospital Administration, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
  4. 4AI Incubation Farm, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
  5. 5Department of Sports and Regenerative Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
  6. 6Department of Orthopedics, Juntendo University Faculty of Medicine, Bunkyo-ku, Japan
  7. 7Department of Medical Technology Innovation Center, Juntendo University, Bunkyo-ku, Japan
  8. 8University of South Florida College of Medicine, Tampa, Florida, USA
  1. Correspondence to Dr Takenori Inomata, Department of Ophthalmology, Juntendo University, Bunkyo-ku, 113-8421, Japan; tinoma{at}juntendo.ac.jp

Abstract

Background/aims This study aimed to assess the efficacy and sterility of stored platelet-rich plasma (PRP) eye-drops for corneal epithelial wound healing compared with those of autologous serum (AS) eye-drops.

Methods At our single institution, PRP and AS eye-drops were prepared using peripheral blood obtained from six healthy volunteers and stored at 4°C. Platelet and leucocyte counts and transforming growth factor (TGF)-β1, epidermal growth factor (EGF), and fibronectin levels were assessed during storage for up to 4 weeks. Sterility was assessed by culturing 4-week poststorage samples. PRP, AS, and phosphate-buffered saline (PBS) eye-drop efficacies were compared using corneal epithelial wound healing assays in vitro and in vivo and monitoring wound areas under a microscope every 3 hours.

Results Higher platelet and lower leucocyte counts were seen in PRP than in whole blood on the day of preparation. After storage, TGF-β1, EGF, and fibronectin levels were significantly higher in PRP than in AS eye-drops. In vitro and in vivo, PRP eye-drops used on the day of preparation significantly promoted corneal epithelial wound healing compared with PBS. Moreover, PRP eye-drops stored for 4 weeks significantly promoted corneal wound healing compared with PBS and AS eye-drops.

Conclusion PRP eye-drops stored at 4°C for 4 weeks promoted corneal epithelial wound healing with higher levels of growth factors than those observed in AS eye-drops, while maintaining sterility, suggesting that this preparation satisfies the unmet medical needs in the treatment of refractory keratoconjunctival epithelial disorders.

  • Cornea
  • Experimental - animal models
  • Experimental - laboratory
  • Ocular surface
  • Wound healing

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information. The authors confirm that the data supporting the findings of this study are available within the article and/or its online supplemental materials.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information. The authors confirm that the data supporting the findings of this study are available within the article and/or its online supplemental materials.

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Footnotes

  • Contributors YO and TI had full access to all the data in this study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: YO, TI, JZ, YS, YK, MN, and HN. Acquisition, analysis or interpretation of data: YO, KeiF, KenF, JZ, AY, HS, AM-I, AE, KN, YA, KH, TH, and MK. Drafting of manuscript: YO, TI, and JS. Critical revision of the manuscript for important intellectual content: TI, KeiF, KenF, HS, YS, YK, MN, HN, and AM. Obtained funding: YO, TI, KeiF, and HS. Statistical analysis: YO, TI, AMI, and KN. Administrative, technical or material support: TI, MN, and AM. Supervision: TI and AM. Guarantor of work: TI.

  • Funding This work was partly supported by a Grant-in-Aid for Special Research in Subsidies for ordinary expenses of private schools from The Promotion and Mutual Aid Corporation for the Private Schools of Japan (Grant Number: none, TI), JSPS KAKENHI Grant Numbers 21K20997 (YO), 20K09810 (TI), 20K22985 (KeiF), 21K16884 (KenF) and 21K20996 (HS).

  • Competing interests YO, TI,and AM have a patent pending for the manufacturing method of PRP eye-drops (pending patent application 2020-164360).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.