title: Kinetics of Angiogenic Responses in Corneal Transplantation.
abstract: OBJECTIVE
  To delineate and compare the kinetics of corneal angiogenesis after high-risk (HR) versus low-risk (LR) corneal transplantation.
  
  
  METHODS
  In mice, intrastromal sutures were placed in the recipient graft bed 2 weeks before allogeneic transplantation to induce angiogenesis and amplify the risk of graft rejection. Control (LR) graft recipients did not undergo suture placement, and thus the host bed remained avascular at the time of transplantation. Graft hemangiogenesis and opacity scores were evaluated for 8 weeks by slit-lamp biomicroscopy. Immunohistochemistry was used to measure CD31 (blood vessels) and LYVE-1 (lymphatic vessels) cells.
  
  
  RESULTS
  Biphasic kinetics were observed for hemangiogenesis in both HR and LR transplant recipients using clinical and immunohistochemical assessments. The biphasic kinetics were composed of a rise-fall (phase 1) followed by a second rise (phase 2) in the degree of vessels. Compared with LR recipients, HR recipients showed higher hemangiogenesis (whole cornea and graft) throughout 8 weeks. Analyzing grafts revealed sustained presence of lymphatic vessels in HR recipients; however, lymphatic neovessels regressed in LR recipients 2 weeks posttransplantation. In contrast to HR host beds, the LR host bed microenvironment cannot sustain the growth of lymphatic neovessels in allografts, whereas it can sustain continued hemangiogenesis.
  
  
  CONCLUSIONS
  The sustained presence of lymphatic vessels in HR host beds can facilitate host immunity against allografts and is likely associated with ongoing higher risk of rejection of these grafts in the long term, suggesting that therapeutic interventions targeting inflammation and lymphatic vessels need to be sustained long term in the HR corneal transplant setting.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA.
authors.forename: Takenori
authors.initials: T
authors.lastname: Inomata
authors.forename: Alireza
authors.initials: A
authors.lastname: Mashaghi
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Zazzo
authors.forename: Sang-Mok
authors.initials: SM
authors.lastname: Lee
authors.forename: Homer
authors.initials: H
authors.lastname: Chiang
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D003315:Cornea / Q000098:blood supply*; D016510:Corneal Neovascularization / Q000378:metabolism* / Q000473:pathology; D016039:Corneal Transplantation; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D006023:Glycoproteins / Q000378:metabolism; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000378:metabolism* / Q000473:pathology; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C492273:LYVE1 protein, mouse