Abstract
Purpose: :
The process of new lymphatic vessel growth (lymphangiogenesis) is associated with poor prognosis in corneal transplants and other inflammatory disorders of the cornea. The fate of newly synthesized lymphatic vessels induced by inflammation is poorly understood. To address this question we designed experiments to determine the fate of newly synthesized lymphatic vessels in the context of corneal recovery after an inflammatory response.
Methods: :
A suture removal modification was used to induce corneal recovery after suture induced inflammation. We measured corneal thickness, leukocyte infiltrate, and pro-inflammatory cytokines as indictors of corneal inflammation and recovery. Lymphatic vessels and MHC-II positive leukocytes were visualized using immunofluorescent microscopy techniques in whole mount cornea. Lymphatic vessel density, sprouting, and trafficking of MHC-II positive cells were quantified.
Results: :
We identified an increase in markers of corneal inflammation in sutured cornea that resolved 14 days after suture removal. Corneal suture placement induced sprouting lymphatic vessels with the capacity to transport MHC-II positive leukocytes. Following suture removal and recovery, regressed lymphatic vessels were thin and fragmented, had bulbous termini, discontinuous expression of CD31 and VE-cadherin, and excluded MHC-II positive leukocytes. In addition to lymphatic vessel fragments, we detected individual lymphatic endothelial cells with decreased LYVE-1 and/or CD31 expression.
Conclusions: :
Functionally distinct regressed lymphatic vessels developed during corneal repair. The balance of lymphatic vessel growth and regression is likely to play a central role in the pathogenesis of many corneal inflammatory diseases. We submit that lymphatic vessel regression is a critical component during corneal repair and that perturbations of this process may be pro-inflammatory and contribute to chronic or recurrent inflammatory conditions of the cornea.
Keywords: cornea: basic science • wound healing • pathology: experimental