PMID- 35533080
OWN - NLM
STAT- MEDLINE
DCOM- 20220511
LR  - 20220716
IS  - 2164-2591 (Electronic)
IS  - 2164-2591 (Linking)
VI  - 11
IP  - 5
DP  - 2022 May 2
TI  - Posttransplant VEGFR1R2 Trap Eye Drops Inhibit Corneal (Lymph)angiogenesis and 
      Improve Corneal Allograft Survival in Eyes at High Risk of Rejection.
PG  - 6
LID - 10.1167/tvst.11.5.6 [doi]
LID - 6
AB  - PURPOSE: To assess whether topical application of VEGFR1R2 Trap after corneal 
      transplantation can impair corneal (lymph)angiogenesis and promote murine corneal 
      allograft survival in eyes at high risk of rejection. METHODS: We used the murine 
      model of suture-induced neovascularization and subsequent keratoplasty in eyes at 
      high risk of rejection, which is an established model for local drug application. 
      After transplantation, the mice were treated with either VEGFR1R2 Trap 
      (aflibercept) or human IgG Fc as eye drops for 2 weeks (three times/d). 
      Deposition of VEGFR1R2 Trap in corneal tissue was detected by 
      immunohistochemistry. Two and 8 weeks after transplantation, corneal 
      (lymph)angiogenesis was assessed morphometrically. Dendritic cells (DCs) and 
      regulatory T cells (Tregs) in the draining lymph nodes (dLNs) were examined by 
      flow cytometry. Allograft survival was determined by corneal graft opacity 
      scores. RESULTS: Topically applied VEGFR1R2 Trap penetrated into corneal host and 
      graft stroma after keratoplasty in eyes at high risk of rejection. Additional 
      postsurgical corneal hemangiogenesis (P < 0.0001) and lymphangiogenesis (P < 
      0.01) as well as infiltrating CD45+ leukocytes (P < 0.001) and macrophages (P < 
      0.01) were significantly reduced in the VEGFR1R2 Trap group compared to controls. 
      VEGFR1R2 Trap eye drops significantly decreased the frequency of total CD11c+ DCs 
      (P < 0.01), as well as activated CD11c+MHC II+ DCs (P < 0.01) and CD11c+CD40+ DCs 
      (P < 0.05). In contrast, the frequency of CD200R+ regulatory DCs (P < 0.05) and 
      Tregs in dLNs (P < 0.01) was enhanced. Moreover, long-term allograft survival was 
      also improved (P < 0.05). CONCLUSIONS: Temporary, topical application of VEGFR1R2 
      Trap after corneal transplantation can achieve sufficient anti-VEGF activity, 
      inhibit additional (lymph)angiogenesis, and significantly improve corneal 
      allograft survival in eyes at high risk of rejection. TRANSLATIONAL RELEVANCE: 
      VEGFR1R2 Trap eye drops after transplantation present a new therapeutic option 
      for patients undergoing corneal transplantation and are at high risk of graft 
      rejection.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Ophthalmology, University of Cologne, Faculty of Medicine and 
      University Hospital Cologne, Cologne, Germany.
FAU - Schonberg, Alfrun
AU  - Schonberg A
AD  - Department of Ophthalmology, University of Cologne, Faculty of Medicine and 
      University Hospital Cologne, Cologne, Germany.
FAU - Bock, Felix
AU  - Bock F
AD  - Department of Ophthalmology, University of Cologne, Faculty of Medicine and 
      University Hospital Cologne, Cologne, Germany.
AD  - Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, 
      Germany.
FAU - Cursiefen, Claus
AU  - Cursiefen C
AD  - Department of Ophthalmology, University of Cologne, Faculty of Medicine and 
      University Hospital Cologne, Cologne, Germany.
AD  - Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transl Vis Sci Technol
JT  - Translational vision science & technology
JID - 101595919
RN  - 0 (Ophthalmic Solutions)
SB  - IM
MH  - Animals
MH  - *Corneal Transplantation
MH  - *Graft Survival
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Neovascularization, Pathologic
MH  - Ophthalmic Solutions/pharmacology
PMC - PMC9100603
COIS- Disclosure: W. Zhang, None; A. Schonberg, None; F. Bock, None; C. Cursiefen, None
EDAT- 2022/05/10 06:00
MHDA- 2022/05/12 06:00
PMCR- 2022/05/09
CRDT- 2022/05/09 12:33
PHST- 2022/05/09 12:33 [entrez]
PHST- 2022/05/10 06:00 [pubmed]
PHST- 2022/05/12 06:00 [medline]
PHST- 2022/05/09 00:00 [pmc-release]
AID - 2778811 [pii]
AID - TVST-21-4301 [pii]
AID - 10.1167/tvst.11.5.6 [doi]
PST - ppublish
SO  - Transl Vis Sci Technol. 2022 May 2;11(5):6. doi: 10.1167/tvst.11.5.6.