Intraocular injection of tamoxifen‐loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitis
Open accessAbstract
In this study, we tested the efficiency of an intravitreal injection of tamoxifen, a non‐steroidal estrogen receptor modulator, in retinal soluble antigen (S‐Ag)‐induced experimental autoimmune uveoretinitis (EAU). To increase the bioavailability of tamoxifen, we incorporated tamoxifen into polyethylene glycol (PEG)‐coated nanoparticles (NP‐PEG‐TAM). The localization of the nanoparticles within the eye was investigated using fluorescent‐labeled PEG‐coated nanoparticles after injection into the vitreous cavity of rats with EAU. Some nanoparticles were distributed extracellularly throughout the ocular tissues, others were concentrated in resident ocular cells and in infiltrating macrophages. Whereas the injection of free tamoxifen did not alter the course of EAU, injection of NP‐PEG‐TAM performed 1–2 days before the expected onset of the disease in controls resulted in significant inhibition of EAU. NP‐PEG‐TAM injection significantly reduced EAU compared to injection of NP‐PEG‐TAM with 17β‐estradiol (E2), suggesting that tamoxifen is acting as a partial antagonist to E2. Diminished infiltration by MHC class II+ inflammatory cells and low expression of TNF‐α, IL‐1β, and RANTES mRNA were noted in eyes of NP‐PEG‐TAM‐treated rats. Intravitreal injection of NP‐PEG‐TAM decreased S‐Ag lymphocyte proliferation, IFN‐γ production by inguinal lymph node cells, and specific delayed‐type hypersensitivity indicative of a reduced Th1‐type response. It increased the anti‐S‐Ag IgG1 isotype indicating an antibody class switch to Th2 response. These data suggest that NP‐PEG‐TAM inhibition of EAU could result from a form of immune deviation. Tamoxifen‐loaded nanoparticles may represent a new option for the treatment of experimental uveitis.
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Similar results have been shown for other proteins in rats and rabbits, where intravitreal injection of retinal soluble antigen or human serum albumin resulted in an increase in anti-antigen antibodies in serum.
“Similar results have been shown for other proteins in rats and rabbits, where intravitreal injection of retinal soluble antigen or human serum albumin resulted in an increase in anti-antigen antibodies in serum.63,64”
From Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates (2015) · cites this paper as [63]
The Results (§2.6.4 Serum antibody isotypes; page unavailable) report increased serum anti-S-Ag IgG1 in rats after intravitreal injection of tamoxifen-loaded nanoparticles. But the Methods (§4.2 Induction of EAU) say S-Ag was administered into the hind footpads, not injected intravitreally. The paper does not report an intravitreal human-serum-albumin experiment in rabbits. (LLM, conf=0.87)
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- Authors
- de Kozak, Y., Andrieux, K., Villarroya, H., Klein, C., Thillaye‐Goldenberg, B., Naud, M., Garcia, E., & Couvreur, P.
- Affiliations
- Université Paris-Sud (FR)
- Inserm (FR)
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2004-11-26
- Volume
- 34
- Issue
- 12
- Pages
- 3702-3712
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2067144113
- Cited by
- 130
- References
- 39
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 6 · 2016: 8 · 2015: 7 · 2014: 15 · 2013: 4 · 2012: 10
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- Retina France
- Topics
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- tamoxifen, PEG-coated nanoparticles, experimental autoimmune uveoretinitis, intravitreal injection, estrogen receptor modulators, estradiol, uveitis treatment, cytokine expression, delayed-type hypersensitivity
- MeSH terms
- Animals, Immunohistochemistry, Injections, Retina, Retinitis, Tamoxifen, Time Factors, Uvea, Uveitis, Cytokines, Selective Estrogen Receptor Modulators, Nanotubes, Rats
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