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J. Schwartzkopff, M. Berger, I. Gross, P. Eberwein, F. Birnbaum, T. Reinhard; Accelerated Corneal Allograft Rejection in Young versus Mature Rats. Invest. Ophthalmol. Vis. Sci. 2007;48(13):198.
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Graft survival of corneal allografts was compared clinically and histologically between young and mature rats.
Allogenic penetrating keratoplasty was performed between Lewis recipient and Fisher donor rats. Four combinations were examined: Group 1: Adult Fisher donors and adult Lewis recipients. Group 2: Adult Fisher donors and immature Lewis recipients. Group 3: Adult Lewis donors and recipients. Group 4: Adult Lewis donors and immature Lewis recipients. Clinical evaluations were performed every third day according to an international scoring system, looking at opacity, oedema and vascularisation. Mean transplant survival times were evaluated according to Kaplan-Meier. Eyes with corneal transplants were enucleated at the time of rejection and were stained histologically for cellular infiltrates (CD4+ and CD8+ T cells, NK cells, macrophages and dendritic cells).
All transplants of group 1 were rejected with a mean survival time of 15 days. By contrast, animals of group 2 rejected with a mean survival time of 9 days. Neither group 3 nor 4 showed any sign of rejection. The difference between the mean survival times of groups 1 and 2 was highly significant (p<0,01). All animals of group 2 showed a dense infiltrate on day 9 postoperatively, whereas only a few cells were found in group 1 at that time. In both groups, T cells dominated on the day of rejection, but no differences were found in the ratio between T cells and infiltrating mononuclear cells at that time. The number of infiltrating cells peaked on day 15 in groups 1 and 2 and declined thereafter. However, significantly more macrophages and NK cells were stained in group 2 compared to 1 15 days postoperatively. Groups 3 and 4 showed almost no cellular infiltrates.
This model of keratoplasty in infants provides evidence that graft failure occurs statistically significantly faster in immature rats. Leukocytes infiltrate earlier in this group and increase thereafter, whereas in adults maximal infiltration reflects the time of graft failure. Thus, in young rats already fewer infiltrating cells lead to rejection of the transplanted cornea when compared to adults. The exact mechanism of the rejection process remains unclear, but further experimental evaluations are in progress.
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