Regressed lymphatic vessels develop during corneal repair

Abstract

The fate of newly synthesized lymphatic vessels induced by inflammation is poorly understood. To address this question, we designed experiments to determine the morphologic, phenotypic, and functional differences in regressing lymphatic vessels in the context of corneal recovery after an inflammatory response. A suture removal modification was used to induce corneal recovery after suture induced inflammation. We identified an increase in markers of corneal inflammation in sutured cornea that resolved in 14 days after suture removal. Sprouting newly synthesized lymphatic vessels trafficking MHC-II-positive leukocytes were visualized in sutured cornea. Following suture removal and recovery, the visualized lymphatic vessels were thin and fragmented, had bulbous termini, discontinuous expression of CD31 and VE-cadherin, and excluded MHC-II-positive leukocytes. VEGF-A, VEGF-C, and TGF-β mRNA levels were increased during corneal recovery, suggesting a complex interaction between lymphangiogenic factors and the mechanisms that regulate corneal recovery. The balance of lymphatic vessel growth and regression is likely to have a central role in the pathogenesis of corneal inflammatory diseases.