Related Experiment Video
Updated: Apr 19, 2026
Murine Corneal Transplantation: A Model to Study the Most Common Form of Solid Organ Transplantation
Published on: November 17, 2014
Subconjunctivally applied naïve Tregs support corneal graft survival in baby rats
Antonia Hildebrand1, Christian Jarsch2, Yvonne Kern2
1University Eye Hospital, Killianstrasse 5, 79106 Freiburg, Germany ; Faculty of Biology, Albert-Ludwigs-University Freiburg, Germany.
Insights
Local application of regulatory T cells (Tregs) can prevent corneal graft rejection in young infants. This study shows subconjunctival Treg administration is more effective than systemic delivery in a baby rat model.
Area of Science:
- Immunology
- Ophthalmology
- Transplantation Science
Background:
- Corneal transplantation is successful in adults but faces high rejection rates (up to 85%) in infants younger than 12 months.
- Immunosuppressive therapy is challenging in young children, necessitating alternative strategies to prevent lifelong visual impairment from corneal opacity.
Purpose of the Study:
- To investigate the role of naive regulatory T cells (Tregs) in juvenile corneal transplantation.
- To evaluate the efficacy of unprimed Tregs in preventing accelerated graft rejection in a baby rat keratoplasty model.
Main Methods:
- Studied Treg counts and inhibitory potential in 3- and 10-week-old rats.
- Administered unprimed Tregs (CD4+CD25+) systemically or subconjunctivally in allogenic keratoplasty models.
- Analyzed transforming-growth-factor beta (TGF-β) transcription in subconjunctival tissue.
Main Results:
- Treg counts were comparable between age groups, with both showing in vitro inhibitory potential.
- Systemic Treg administration did not significantly delay rejection.
- Subconjunctival Treg application abrogated rejection in 66.7% of 3-week-old and 33.3% of 10-week-old recipients.
Conclusions:
- Local administration of unprimed Tregs shows promise for preventing corneal graft rejection.
- Subconjunctival delivery of Tregs is a potential therapeutic strategy for young corneal transplant recipients.
Purpose:
Corneal transplantation is the most frequent and successful form of tissue transplantation in adults (<10% rejection). In young children, any corneal opacity should be corrected as early as possible to prevent lifelong visual impairment. However, the corneal graft rejection rate is dramatically increased in infants younger than 12 months of age (up to 85% rejection), and immunosuppressive therapy is particularly challenging in this age group. Regulatory T cells (Tregs) are a well-characterized T cell subpopulation with the potential to prevent autoimmune disorders or transplant rejection. Antigen-specific Tregs were shown to inhibit graft rejection in adult stem cell transplantation. Less is known about the role of naïve Tregs.The purpose of the present study was to elucidate the relevance of naïve Tregs in juvenile corneal transplantation in a baby rat keratoplasty model that reproduces the accelerated rejection in young patients.
Methods:
Counts and inhibitory potential of Tregs were studied in spleens of 3- and 10-week-old rats. Unprimed Tregs (CD4+CD25+) were isolated from the spleens of 10-week-old Lewis rats and systemically or subconjunctivally administered in vivo in allogenic keratoplasty in 3- and 10-week-old Lewis recipient rats. In subconjunctival tissue, transcription was analyzed for induction of transforming-growth-factor beta (TGF-β).
Results:
In 3-week-old rats, CD4 T cell counts, but not FoxP3 T cell counts were lower than in 10-week-old rats. The Tregs of both age groups had the potential to inhibit T cell activation in vitro. No significant delay in rejection was observed when Tregs were applied systemically before keratoplasty. However, subconjunctival application of Tregs abrogated rejection in 66.7% and 33.3% of the 3- and 10-week-old recipients, respectively. Analysis of the conjunctival tissue revealed a transplantation-induced increase in TGF-β transcription in the 3-week-old rats.
Conclusions:
Our data suggest that local application of unprimed regulatory T cells may be a therapeutic strategy for preventing corneal graft rejection in young recipients.
More Related Videos
11:20Retinal Pigment Epithelium Transplantation in a Non-human Primate Model for Degenerative Retinal Diseases
Published on: June 14, 2021
11:03Subretinal Transplantation of Human Embryonic Stem Cell Derived-retinal Pigment Epithelial Cells into a Large-eyed Model of Geographic Atrophy
Published on: January 22, 2018