Characterization Of The Ocular Immune Response In A Rodent Model Of Whole Eye Transplantation
Bing Li, MD1,2, Yong Wang, MD1, Charles Owens, BS1, Wenshen Zhang, PhD3, Touka Banaee, MD3, Wendy Chen, MD3, Chiaki Komatsu, MD3, Ariel Johnson, BS1, An-jey Su, PhD1, Mario Solari, MD3, David Mathes, MD1, Christene A. Huang, PhD1, Kia Washington, MD1.
1University of Colorado, Aurora, CO, USA, 2First Hospital of Jilin University, Changchun, China, 3University of Pittsburgh, Pittsburgh, PA, USA.
Approximately 36 million people throughout the world suffer from blindness. Whole eye transplantation (WET) may offer a potential solution to restore lost vision, in particular in the setting of ocular trauma. As a vascularized composite allograft (VCA), the complex multi-tissue structure of WET is predicted to be highly immunogenic with potential for high incidence of graft rejection. Unlike most VCA, however, WET also contains a blood ocular barrier with potential to insulate parts of the eye graft from the host immune system. This combination of high tissue immunogenicity and potential special immune privilege property make WET a unique allograft for immunological study. We performed orthotopic rodent WET across syngeneic and fully MHC mismatched barriers without any immunosuppression to characterize the immune reaction and rejection response following WET for the first time.
14-wk old male Brown Norway (BN) rats served as donor and recipient in the syngeneic group (S-group). 14-wk old male BN rats served as donors with age/sex matched Lewis rats used as recipient in the allogeneic group (A-group). 6 na´ve rats were used as a control group (C-group). After WET, skin and cornea rejection at POD 2, 4, 5, 6, 8 were assessed by the Banff based scoring system. Gene expression associated with rejection was measured by qPCR of eye tissue for all groups on POD5. Serum cytokine/ chemokine levels were tested by ELISA.
At POD5 allogeneic corneas had transparency changes that coincided with skin rejection and Cornea thickness dramatically increased by 150% over syngeneic eyes. qPCR revealed significant upregulation of genes associated with classic T-cell mediated adaptive immunity. Serum IFN-γ increased rapidly on POD5 then returned to basal levels by POD6 in allogeneic non-immunosuppressed animals.
Our results suggest that A typical T cell-mediated acute adaptive immune response occurred after allogeneic whole eye transplantation. Changes of cornea transparency and serum IFN-γ level can be used to diagnose and monitor rejection episode. Cornea change is more sensitive than skin change for rejection diagnosis.
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