Alkali injury–induced pathological lymphangiogenesis in the iris facilitates the infiltration of T cells and ocular inflammation
Zheng Liu, Keli Liu, Shunhua Shi, Xun Chen, Xinyu Gu, Weifa Wang, Keli Mao, Rukeye Yibulayi, Wanwen Wu, Lei Zeng, Weibin Zhou, Xiaofeng Lin, Feng Zhang, Bingsheng Lou
Zheng Liu, Keli Liu, Shunhua Shi, Xun Chen, Xinyu Gu, Weifa Wang, Keli Mao, Rukeye Yibulayi, Wanwen Wu, Lei Zeng, Weibin Zhou, Xiaofeng Lin, Feng Zhang, Bingsheng Lou
View: Text | PDF
Research Article Immunology Ophthalmology

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

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.

Authors

Zheng Liu, Keli Liu, Shunhua Shi, Xun Chen, Xinyu Gu, Weifa Wang, Keli Mao, Rukeye Yibulayi, Wanwen Wu, Lei Zeng, Weibin Zhou, Xiaofeng Lin, Feng Zhang, Bingsheng Lou

×

Figure 6

Inhibition of lymphangiogenesis alleviates CAI-induced retinal edema and enlargement of cervical lymph nodes.

Options: View larger image (or click on image) Download as PowerPoint
Inhibition of lymphangiogenesis alleviates CAI-induced retinal edema and...
(A) Experimental timeline of TAM administration CAI in B–F. Mice received CAI or sham treatment at week 6, followed by TAM administered 5 times (80 mg/kg) i.p. between days 13 and 17 and analysis on day 28 after CAI. (B) Histological assessment of CAI-induced retina edema. Shown are representative images of the optic disc, peri-disc, middle, and peripheral regions in cross-sectioned retinas from VEGFR3iLECko and VEGFR3fl/fl mice with CAI or sham treatment. Scale bar: 50 μm. GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer. (C) Quantitation of thickness of the peri-disc, middle, and peripheral retinal regions in B. Data are shown as mean ± SEM. n = 4 mice per group. Each dot represents 1 mouse. *P < 0.05, **P < 0.01. One-way ANOVA with the Tukey post hoc test. (D) Quantitation of GCL, INL, and ONL thickness in the peri-disc, middle, and peripheral retinal regions in B. Data are shown as mean ± SEM. n = 4 mice per group. Each dot represents 1 mouse. *P < 0.05, **P < 0.01. One-way ANOVA with the Tukey post hoc test. (E and F) Images and the average diameter of cervical lymph nodes from VEGFR3iLECko and VEGFR3fl/fl mice with CAI or sham treatment. Scale bar: 2 mm. Data are shown as mean ± SEM. Each dot represents the average diameter of lymph nodes obtained from 1 mouse. n = 4 mice per group. *P < 0.05. Mann-Whitney U test.