Accelerated corneal graft rejection in baby rats

Schwartzkopff, Johannes; Berger, Moritz; Birnbaum, Florian; Böhringer, Daniel; Reinhard, Thomas

doi:10.1136/bjo.2008.154435

Cited by 17 publications

(23 citation statements)

References 24 publications

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“…Corneal transplantation in pre-sensitized hosts with surface inflammation, in emergency situations [11], in very young recipients [12,13] or in patients with allergic or atopic afflictions [14,15] shows a higher rate of immune reactions leading to graft failure. Compared to low-risk situations, these patients require systemic immunosuppressive therapy with cyclosporin A or mycofenolate mofetile [10,14] in addition to topical corticosteroids.…”

Section: Introductionmentioning

confidence: 99%

“…Most recently, the beneficial effect of AZM was reported in a mouse model of corneal transplantation [31]. We studied the effects of topically applied AZM in a well-established rat keratoplasty model [12,18] with a particular emphasis on the adequate time frame for treatment. Our data also supports the use of AZM to prevent corneal graft rejection and we strongly suggest that short-term perioperative application is sufficient to abrogate graft failure.…”

Section: Introductionmentioning

confidence: 99%

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Short-Term Azithromycin Treatment Promotes Cornea Allograft Survival in the Rat

et al. 2013

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BackgroundAny inflammatory response following corneal transplantation may induce rejection and irreversible graft failure. The purpose of this study is to analyze the anti-inflammatory effect of azithromycin (AZM) following experimental keratoplasty in rats.MethodsCorneal transplants were performed between Fisher-donor and Lewis-recipient rats. Recipients were postoperatively treated three times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an additional control, AZM was applied following syngeneic keratoplasty. Furthermore, short-term treatments with AZM for seven days perioperatively or with AZM only three days prior to the transplantation were compared to appropriate controls. All transplants were monitored clinically for opacity, edema, and vascularization. Infiltrating CD45+, CD4+, CD8+, CD25+, CD161+ and CD163+ cells were quantified via immunohistochemistry.ResultsAZM significantly promoted corneal graft survival compared with miglyol or ofloxacin treatment. This effect was comparable to topical dexamethasone. No adverse AZM effect was observed. Histology confirmed a significant reduction of infiltrating leukocytes. The short-term application of AZM for three days prior to transplantation or for seven days perioperatively reduced corneal graft rejection significantly compared with the controls.ConclusionsAlong with antibiotic properties, topical AZM has a strong anti-inflammatory effect. Following keratoplasty, this effect is comparable to topical dexamethasone without the risk of steroid-induced adverse effects. Short-term treatment with AZM three days prior to the transplantation was sufficient to promote graft survival in the rat keratoplasty model. We therefore suggest further assessing the anti-inflammatory function of topical AZM following keratoplasty in humans.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Short-Term Azithromycin Treatment Promotes Cornea Allograft Survival in the Rat

et al. 2013

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“…The upregulation of galectin-9 may dampen inflammation in the corneal allografts by promoting Treg cell polarization 26 and impairing the functions of natural killer cells, 27 which are also involved in corneal allograft rejection. 28 Notably, in control corneas, galectin-9 is mainly expressed in the epithelium. It has been reported that although corneal epithelium express over 90% of the major histocompatibility complex (MHC) antigens, removal of corneal epithelium does not enhance corneal graft survival in humans and even appears to exacerbate corneal allograft rejection in mice, 29-31 suggesting the corneal epithelium suppresses inflammation and neovascularization in corneal allografts.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Galectin Expression Signatures in Rejected and Accepted Murine Corneal Allografts

Sugaya

Chen

Cao

et al. 2015

Cornea

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Purpose Although members of the galectin family of carbohydrate-binding proteins are thought to play a role in the immune response and regulation of allograft survival, little is known about the galectin expression signature in failed corneal grafts. The goal of this study is to compare the galectin expression pattern in accepted and rejected murine corneal allografts. Method Using BALB/c mice as recipients and C57BL/6 mice as donors, a total of 57 transplants were successfully performed. One week after transplantation, the grafts were scored for opacity by slit-lamp microscopy. Opacity scores of 3+ or greater on postoperative week 4 were considered rejected. Grafted corneas were harvested on postoperative week 4, and their galectin expression was analyzed by Western blot and immunofluorescence staining. Result As determined by Western blot analyses, galectins-1, -3, -7, -8 and -9 were expressed in normal corneas. Although in both accepted and rejected grafts, expression levels of the five lectins were upregulated compared to normal corneas, there were distinct differences in the expression levels of galectins-8 and -9 between accepted and rejected grafts, as both Western blot and immunofluorescence staining revealed galectin-8 is upregulated, whereas galectin-9 is downregulated in rejected grafts compared to accepted grafts. Conclusion Our findings that corneal allograft rejection is associated with an increased galectin-8 expression and a reduced galectin-9 expression, support the hypothesis that galectin-8 may reduce graft survival, whereas galectin-9 may promote graft survival. As a potential therapeutic intervention, inhibition of galectin-8 and/or treatment with exogenous galectin-9 may enhance corneal allograft survival rates.

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“…[16][17][18] More recently, it was also reported that corneal grafts in infant rats were rejected at an accelerated rate. 19 Center for Eye Disease and Development, Program in Vision Science, School of Optometry, University of California, Berkeley, California. This study is supported in part by research grants from National Institutes of Health, Department of Defense, and the University of California at Berkeley.…”

Section: Introductionmentioning

confidence: 99%

Increased Lymphangiogenesis and Hemangiogenesis in Infant Cornea

Yuen

Leu

Sadovnikova

et al. 2011

Lymphatic Research and Biology

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Background: Corneal lymphangiogenesis (LG) and hemangiogenesis (HG) accompany many diseases after inflammatory, infectious, traumatic or chemical insults. They also contribute to transplant rejection. It is known that corneal transplants in infants or children have a higher rejection rate than in adults. However, it has never been studied whether infant corneas differ from adult corneas in inflammatory LG, HG, or both, which is the focus of this study. Methods and Results: Corneal inflammatory LG and HG were induced by a standard suture placement model in C57BL/6 mice of 3 weeks and 8 weeks of age, respectively. Corneal LG, HG, and macrophage infiltration were assessed by immunofluorescent microscopic studies using specific antibodies against CD31 (a panendothelial cell marker), LYVE-1 (a lymphatic marker), and F4/80 (a macrophage marker). Blood vessels were also examined by ophthalmic slit-lamp microscopic assays in vivo. Digital images were analyzed by NIH Image J software. It was found, for the first time, that infant corneas exhibited a higher level of LG, HG, and macrophage infiltration during inflammation. Infant lymphatic and blood vessels demonstrated greater density and invasion area but similar branching points. Additionally, infant lymphatic vessels were also of larger diameter. Conclusions: Infant and adult corneas differ greatly in their inflammatory responses of LG, HG, and macrophage infiltration. These novel findings will shed some light on our understanding of the LG and HG processes, as well as the development of new therapeutic protocols for corneal diseases, particularly, in infants or children, where an early restoration of sight is critically important in preventing amblyopia or permanent vision loss.

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Accelerated corneal graft rejection in baby rats

Cited by 17 publications

References 24 publications

Short-Term Azithromycin Treatment Promotes Cornea Allograft Survival in the Rat

Short-Term Azithromycin Treatment Promotes Cornea Allograft Survival in the Rat

Comparison of Galectin Expression Signatures in Rejected and Accepted Murine Corneal Allografts

Increased Lymphangiogenesis and Hemangiogenesis in Infant Cornea

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