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. 2025 Jun;103(4):e220-e230.
doi: 10.1111/aos.17457. Epub 2025 Feb 6.

VEGFR3 pathway in corneal transplantation

Mariateresa Laborante  1   2 , Alessandra Micera  3 , Daniele Gaudenzi  1   2 , Andrea De Luca  1   2 , Chiara De Gregorio  1   2 , Francesco Cutrupi  1   2 , Graziana Esposito  3 , Bijorn Omar Balzamino  3 , Antonio Laborante  4 , Marco Coassin  1   2   5 , Antonio Di Zazzo  1   2   5
Affiliations

VEGFR3 pathway in corneal transplantation

Mariateresa Laborante et al. Acta Ophthalmol. 2025 Jun.

Abstract

Purpose: Corneal transplantation, a common procedure in ophthalmology, faces challenges in high-risk (HR) cases due to inflammation and vascularization of the host bed, leading to graft rejection. Despite advancements in surgical techniques and therapeutics, preventing rejection in HR cases remains elusive. This study investigates the role of the vascular endothelial-derived growth factor (VEGF)-C/D-VEGFR3 pathway in corneal transplantation, focusing on its impact on inflammation and immune response.

Methods: In this study, 42 eyes of 42 patients were evaluated, 24 of whom underwent corneal transplantation, with follow-up visits at 90, 180 and 360 days post-transplantation. Clinical assessments included visual acuity, corneal oedema, endothelial cell count and vascularization. Molecular analyses were performed to measure VEGFR3, VEGF-C, VEGF-D, VEGF-A and inflammatory markers.

Results: Results revealed a distinct pattern of VEGF-C/D and VEGFR3 expression in HR versus low-risk (LR) transplants, correlating with inflammatory markers and clinical outcomes. In HR cases, elevated VEGFR3 expression was associated with increased inflammatory markers (Intercellular Adhesion Molecule 1 (ICAM-1) and Human Leukocyte Antigen - DR isotype (HLA-DR)) and graft rejection risk.

Conclusion: These findings underscore the importance of understanding the VEGF-C/D-VEGFR3 pathway in modulating immune responses and inflammation in corneal transplantation, particularly in HR cases. Targeting this pathway could offer novel therapeutic avenues to mitigate inflammation and improve graft survival. Further research is warranted to elucidate the underlying mechanisms and validate these findings, potentially enhancing transplant outcomes, especially in HR patients.

Keywords: VEGFR3; VEGF‐C/D; graft rejection; immune response; transplantation.

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References

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