Subconjunctival aflibercept inhibits corneal angiogenesis and VEGFR-3CD11b cells.

Graefes Arch Clin Exp Ophthalmol

Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Published: December 2024

AI Article Synopsis

  • The study explored how subconjunctival injections of aflibercept impact corneal blood vessel growth and specific immune cells in a mouse model.
  • Aflibercept led to a significant decrease in new blood vessel formation in the cornea compared to a control treatment with saline.
  • The treatment also lowered levels of certain pro-angiogenic and inflammatory markers in the cornea and reduced the presence of VEGFR-3CD11b immune cells without affecting VEGFR-2CD11b cell levels.

Article Abstract

Purpose: This study aimed to investigate the effects of subconjunctival injection of aflibercept, a soluble protein decoy for VEGFR-1 and VEGFR-2, on corneal angiogenesis and VEGFR-expressing CD11b cells in a mouse model of suture-induced corneal neovascularization.

Methods: Corneal neovascularization was induced in BALB/c mice by placing three sutures on the cornea. Immediately after surgery, either 200 µg aflibercept (5 µL) or an equal volume of phosphate-buffered saline (PBS) was administered into the subconjunctival space. Seven days after later, corneal new vessels were quantified through clinical examination and measurement of the CD31-stained area in corneal flat mounts. The levels of pro-angiogenic and inflammatory markers in the cornea were evaluated using RT-qPCR. The percentages of VEGFR-2CD11b cells and VEGFR-3CD11b cells were analyzed in the cornea, blood, and draining cervical lymph nodes (DLNs) using flow cytometry.

Results: Subconjunctival injection of aflibercept significantly reduced the growth of corneal new vessels compared to subconjunctival PBS injection. The mRNA levels of Cd31, vascular growth factors (Vegfc and Angpt1), and pro-angiogenic/inflammatory markers (Tek/Tie2, Mrc1, Mrc2, and Il6) in the cornea were downregulated by subconjunctival aflibercept. Also, the percentage of VEGFR-3CD11b cells in the cornea, blood, and DLNs was decreased by aflibercept, whereas that of VEGFR-2CD11b cells was unaffected.

Conclusion: Subconjunctival aflibercept administration inhibits inflammatory angiogenesis in the cornea and reduces the numbers of cornea-infiltrating and circulating VEGFR-3CD11b cells.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608285PMC
http://dx.doi.org/10.1007/s00417-024-06560-4DOI Listing

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