Abstract
Purpose :
Pathological neovascularization of the corneal recipient is one of the main risk factors for graft rejection after corneal transplantation. This study aims to assess whether topical application of VEGFR1R2 Trap eye drops after corneal transplantation can impair the outgrowth of blood vessels (BVs) and lymphatic vessels (LVs) and promote murine high-risk corneal allograft survival.
Methods :
Topical VEGFR1R2 Trap or human IgG Fc eye drops (as control) were delivered 3 times per day for 2 weeks after murine high-risk corneal transplantation. VEGFR1R2 Trap in corneal tissue after application was detected by immunohistochemistry. Corneas and draining lymph nodes (dLNs) were excised at week 2 and 8 post-transplantation. Corneal BVs and LVs were quantified by immunohistochemistry and morphological assessment. Dendritic cells (DCs) and regulatory T cells (Tregs) in dLNs were analyzed by flow cytometry. Allograft survival was determined by an 8-week evaluation of corneal opacity scores.
Results :
Topically applied VEGFR1R2 Trap penetrated into the corneal bed and graft stroma after high-risk keratoplasty. Additional, postsurgical hemangiogenesis (P<0.0001) and lymphangiogenesis (P<0.01), and infiltration of CD45+ (P<0.001) as well as macrophages (P<0.01) in corneas were significantly reduced in the VEGFR1R2 Trap group compared to controls after transplantation. VEGFR1R2 Trap eye drops significantly decreased the frequency of CD11c+ DCs (P<0.01), MHC II+CD11c+ DCs (P<0.01) and CD40+CD11c+ DCs (P<0.05), and enhanced the frequency of CD200R+ regulatory DCs (P<0.05) and Tregs in dLNs (P<0.01). Moreover, long-term allograft survival was improved (P<0.05).
Conclusions :
Temporary, posttransplant, topical application of VEGFR1R2 Trap eye drops can achieve sufficient anti-VEGF activity, inhibit additional posttransplant hem- and lymphangiogenesis and significantly improve high-risk corneal allograft survival. VEGFR1R2 Trap eye drops post transplantation may become a new therapeutic option for patients undergoing high-risk corneal transplantation.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.