The Ocular Immune Response in a Rodent Model of Whole Eye Transplantation

Abstract

Abstract Introduction Approximately 36 million people are totally blind globally. Using a rodent whole eye orthotopic transplant model (WET), we are investigating a potential clinical treatment to restore vision. Typically, clinical transplantation involves allogeneic individuals and immune rejection is the first obstacle after surgery. Her--e, we use an MHC class I and II mismatched transplant model without immunosuppression to describe for the first time the features of the immune reaction in WET. Methods 14-wk old male Brown Norway (BN) rats served as donor and recipient in the syngeneic group. 14-wk old male BN rats served as donors with age/sex matched Lewis rats used as recipient in the allogeneic group. Both groups underwent WET, subsequently the transplanted eye blood supply and structure were evaluated on post-operative day (POD) 2 by optical coherence tomography (OCT). Skin and cornea rejection at POD 2,4,5,6,8 were assessed separately by a scoring system. The progressive infiltration of immune cells into the eye was evaluated by flow cytometry and histology. Results At POD5 allogeneic corneas had transparency changes that coincided with skin rejection and Cornea thickness dramatically increased by 150% over syngeneic eyes. Also, the allogeneic group had significant CD4+, CD8+ T cells and NK cell infiltration in aqueous humor, iris, retina and choroid with no difference in cornea. Conclusion These preliminary results indicate that acute rejection in WET is T cell mediated and the blood ocular barrier is compromised post-operatively, where immune cells can access the eye. Rejection after WET can be potentially monitored by noninvasive measurement of the cornea thickness or easily accessible aqueous humor.