Abstract
Introduction: :
Corneal neovascularization is a major risk factor for rejection after penetrating keratoplasty. The aim of this study is to characterize how the degree of corneal neovascularization affects cellular composition before transplantation and rejection rates after allogeneic transplantation.
Methods: :
Low high risk (LHR) murine corneal models were generated by placing two full thickness sutures in the superior cornea of C57BL/6 mice, resulting in two to three clock–hours of corneal neovascularization. High–risk (HHR) murine corneal models were generated by placing one tight, full thickness suture in the nasal and temporal cornea resulting in six to twelve clock–hours of neovascularization. Flow cytometry was used to identify overall corneal cellular composition. Immunohistochemistry allowed comparison of the cellular composition in vascularized sections of LHR and HHR corneas. Ten orthotopic allogeneic (Balb/c to C57BL/6) corneal transplants were performed in both LHR and HHR eyes and survival was assessed.
Results: :
Flow cytometry revealed more macrophages (CD11b+) and neutrophils (Ly6+) in HHR corneas compared to LHR corneas. Immunohistochemistry verified these findings with a higher number of macrophages (CD11b+, F4/80+) and neutrophils (NIMPR14+) found in vascularized HHR corneal sections than in LHR corneal sections. HHR eyes experience significantly faster rejection rates after allogeneic corneal transplantation compared to LHR eyes.
Conclusions: :
The degree of corneal neovascularization affects cellular composition with more macrophages and neutrophils found in the stromal bed of eyes with more blood vessels. A higher degree of vascularization has a negative effect on graft survival after corneal transplantation.
Keywords: transplantation • inflammation • immunomodulation/immunoregulation