Determination of the function of lymphangiogenesis in dry eye induced lacrimal glands

Session Details

Session Title: Ocular Pathologies

Session Date/Time: Tuesday 08/09/2015 | 16:30-18:00

Paper Time: 17:14

Venue: Room 1

First Author: : C.Lee SOUTH KOREA

Co Author(s): :    J. Min   A. Yeo   H. Noh   I. Song   W. Choi   H. Lee     

Abstract Details

Purpose:

By using dry eye(DE) mouse model, we aimed to determine the role of HIF-1α and DLL4-NOTCH1 pathway in lymphangiogenesis in lacrimal gland(LG)s of DE.

Setting:

Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.

Methods:

Male C57BL/6 mice were housed in a controlled-environment chamber (CEC) for DE induction. Quantitative RT-PCR (qPCR), immunoblot, and immunofluorescence (IF) staining were used to measure the expression of NOTCH1/DLL4 pathway and lymphangiogenesis at LGs. During DE induction, subjects were administered anti-DLL4 antibody and gamma-secretase inhibitor (GSI) to suppress NOTCH1/DLL4 pathway. The expression of NOTCH1/DLL4 pathway and lymphangiogenesis were evaluated for DE induced HIF-1α conditional knockout (HIF-1α CKO) mice. Infiltration of CD45+ cells in LG was evaluated for each condition using flow cytometry.

Results:

DE induction significantly up-regulated DLL4-NOTCH1 signaling in LGs compared to the control group. Pathways related to lymphangiogenesis were also increased in DE induced LGs. Inhibition of DLL4-NOTCH1 signaling via anti-DLL4 antibody and GSI injection significantly reduced pathways related to lymphangiogenesis in DE induced LGs. Compared to normal DE induced mice, DE induced HIF-1α CKO mice showed significant down-regulation of NOTCH1/DLL4 and lymphangiogenesis related pathways. When NOTCH signaling was inhibited by injecting GSI and anti-DLL4 antibody, or by knocking out HIF-1α gene, CD45+ cell infiltration significantly increased under DE condition compared to normal DE group.

Conclusions:

HIF-1α and DLL4-NOTCH1 pathway are closely related to lymphangiogenesis in DE induced LGs. Lymphangiogenesis stimulated by HIF-1α and NOTCH signaling may play a protective role against inflammation by aiding the clearance of immune cells from DE induced LGs.

Financial Interest:

NONE