Alkali injury-induced pathological lymphangiogenesis in the iris facilitates the infiltration of T cells and ocular inflammation

JCI Insight. 2024 Apr 8;9(7):e175479. doi: 10.1172/jci.insight.175479.

Abstract

Inflammatory lymphangiogenesis is intimately linked to immune regulation and tissue homeostasis. However, current evidence has suggested that classic lymphatic vessels are physiologically absent in intraocular structures. Here, we show that neolymphatic vessels were induced in the iris after corneal alkali injury (CAI) in a VEGFR3-dependent manner. Cre-loxP-based lineage tracing revealed that these lymphatic endothelial cells (LECs) originate from existing Prox1+ lymphatic vessels. Notably, the ablation of iridial lymphangiogenesis via conditional deletion of VEGFR3 alleviated the ocular inflammatory response and pathological T cell infiltration. Our findings demonstrate that iridial neolymphatics actively participate in pathological immune responses following injury and suggest intraocular lymphangiogenesis as a valuable therapeutic target for the treatment of ocular inflammation.

Keywords: Immunology; Lymph; Ophthalmology; Retinopathy; T cells.

MeSH terms

  • Alkalies
  • Corneal Injuries*
  • Endothelial Cells
  • Humans
  • Inflammation
  • Iris
  • Lymphangiogenesis* / physiology
  • T-Lymphocytes

Substances

  • Alkalies

Grants and funding

the Fundamental Research Funds of the State Key Laboratory of Ophthalmology and the High-level Hospital Construction Project of Guangdong Providence