Complement Fragment C4d Deposition Causing Thickening of Descemets Membrane In Corneal Graft Rejection: Animal Model Study

Abstract

Purpose : To evaluate Descemets membrane (DM) characteristics in corneal graft rejection through an animal model and examine obtained DM specimens by immunohistochemistry so as to detect the pathogenesis behind observed changes.

Methods : 18 rats served as an animal model of corneal transplantation. Thirteen rats received allogenic corneal grafts to serve as a model of corneal graft rejection. Another 5 rats received syngeneic corneal grafts in order to be used as a model of successful corneal graft transplant. Contralateral eyes of all rats served as controls. DM thickness was measured by light microscopy. Immunohistochemistry staining of excised tissue was done using a rat monoclonal antibody to C4d. The results were analyzed using paired Student t-test with IBM SPSS.

Results : Rejected corneal grafts had significantly thicker DM compared to the contralateral eyes with mean thickness of 3.38 vs 2.77 μm (p<0.001). Meanwhile, there was no significant difference between accepted grafts and contralateral eyes. Complement fragment C4d depositions were noted in 7 out of 9 rejected corneal grafts and in none of the accepted grafts (P=0.02). Five rats were excluded secondary to infection and surgical failure.

Conclusions : Thickening of the Descemets membrane is observed ex vivo in corneal graft rejection in an animal model, resembling in vivo changes noted in human rejected corneal grafts. Complement fragment C4d deposition were demonstrated in rejected corneal grafts Descemets membrane and could explain the observed pathological thickening of the membrane.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.