Rapamycin nano-micelle ophthalmic solution reduces corneal allograft rejection by potentiating myeloid-derived suppressor cells' function
Open accessAbstract
Allograft rejection is the major cause for corneal graft failure. Rapamycin（RAPA）was reported as an effective and novel immunosuppressive agent for patients undergoing corneal transplantation. However, the high water insolubility and low bioavailability has strongly constrained its clinical application. Here we successfully developed RAPA nano-micelle ophthalmic solution, and found that corneal allograft survival in RAPA nano-micelle ophthalmic solution treated recipients was significantly prolonged for more than 2 months, with less inflammatory infiltration, decreased production of pro-inflammatory factors and elevated recruitment of MDSCs. MDSCs from RAPA nano-micelle ophthalmic solution treated mice could significantly inhibit the proliferation of CD4+T cells with increased expressions of inducible nitric oxidase (iNOS) and arginase-1 (Arg-1). Activity blockade of Arg-1 and iNOS pharmacologically reversed their immunosuppressive ability. Moreover, the effects of RAPA were counterbalanced by the administration of anti-Gr-1 antibody or inhibiting the activity of iNOS pharmacologically. In addition, RAPA nano-micelle also effectively alleviated the allograft rejection in high-risk rabbit PKP models with corneal vascularization. Collectively, our results demonstrated that RAPA nano-micelle ophthalmic solution could improve the immunosuppressive activity of MDSCs through elevated expression of Arg-1 and iNOS, which highlights the possible therapeutic applications of RAPA on corneal allograft rejection.
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Corneal allograft survival in recipients treated with RAPA nano-micelle ophthalmic solution was evidently prolongated for over 2 months, accompanied by decreased inflammatory infiltration and production of pro-inflammatory factors.
“Similarly, investigators demonstrated that corneal allograft survival in recipients treated with a RAPA nano-micelle ophthalmic solution was evidently prolongated for over 2 months, accompanied by decreased inflammatory infiltration and production of pro-inflammatory factors [153]”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [153]
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“Similarly, investigators demonstrated that corneal allograft survival in recipients treated with a RAPA nano-micelle ophthalmic solution was evidently prolongated for over 2 months, accompanied by decreased inflammatory infiltration and production of pro-inflammatory factors [153] (Fig.”
Self-citation
- Authors
- Wei, C., Wang, Y., Ma, L., Wang, X., Chi, H., Zhang, S., Liu, T., Li, Z., Xiang, D., Dong, Y., Wu, X., Shi, W., & Gao, H.
- Affiliations
- Shandong First Medical University (CN)
- University of Jinan (CN)
- Qingdao University (CN)
- Qingdao University of Science and Technology (CN)
- Corresponding author
- Shi, Weiyun
- Gao, Hua
- ORCID
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2018-10-08
- Volume
- 9
- Pages
- 2283-2283
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC6186809
- OpenAlex
- W2897903405
- Cited by
- 38
- References
- 45
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 4
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (20081148, 81500767, 81570821, 2013CB967004, 81530027, 81370989, 2016GSF201182)
- Shandong Academy of Medical Sciences (2013CB967004, 81570821, 20081148, 81530027, 81370989)
- National Key Research and Development Program of China (2013CB967004, 81570821, 20081148, 81370989)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal surgery and disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal Surgery and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- rapamycin, corneal graft rejection, myeloid-derived suppressor cells, immunosuppression, arginase-1, inducible nitric oxide synthase, CD4+ T cell proliferation, corneal transplantation, corneal neovascularization, drug delivery
- MeSH terms
- Myeloid-Derived Suppressor Cells, Animals, Arginase, Eye, Graft Rejection, Immunosuppressive Agents, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Micelles, Ophthalmic Solutions, Rabbits, Keratoplasty, Penetrating, Corneal Transplantation, Sirolimus, Nitric Oxide Synthase Type II, Nanoparticles, Allografts
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