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AbstractDO.18.03 Baby rat model of penetrating keratoplasty Schwartzkopff J., Reinhard T.
University Eye Hospital Freiburg, Germany Objective: Systemic immune reactions are the major cause of corneal graft failure. The immune privilege of the eye contributes to a very high survival rate of more than 90% after penetrating keratoplasty in low risk situations. However, any form of inflammation in the cornea changes these conditions into a high risk situation. Depending on the reason for the elevated immunological risk only 20-70% of clear grafts are seen within the first 5 postoperative years. Contrary to that are clinical observations made in infants under the age of 3 years, where the rejection rate is significantly elevated and only 15-30% of the corneal grafts remain clear. We developed a baby rat model for penetrating keratoplasty as tool to get insight into the immunological mechanisms of corneal graft failure in infant individuals.
Methods: Penetrating keratoplasty was performed between Lewis recipient and Fisher donor rats. The donor's and recipient's age was varied between 10 and 3 weeks, respectively. Postoperatively, the transplants were monitored for opacity, edema and vessel formation. Finally, histological evaluations for mononuclear infiltrates were performed on the day of rejection. In all experimental settings the impact of the recipient's natural killer (NK) cells and the recipient's regulatory T cells was analyzed by either depletion or adoptive transfer experiments. On the other hand, the meaning of corneal antigen presenting cells (APC) was emphasized.
Results: As known from humans below the age of 3 years our rat model provides evidence that graft failure occurred significantly earlier in young rats when compared to old animals. A different cellular infiltrate together with different rejection kinetics clearly demonstrate that disparate mechanisms may be responsible for corneal graft failure in very young individuals. Moreover, a certain meaning of the graft's immunogenicity appeared to be obvious. The results of the depletion, the adoptive transfer and the distribution of corneal APC clearly point to a multifactor scenario that is the topic for further discussion in this symposium.
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