June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Lymphatic Hypoplasia Induced in Mice Reduces Recruitment of Immune Cells to the Ocular Surface in Low-grade Chronic Inflammation Such As Dry Eye
Author Affiliations & Notes
  • Hyun Goo Kang
    Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  • Nayeong Gu
    Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  • Hyung Keun Lee
    Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
    Department of Ophthalmology, Institute of Corneal Dystrophy Research, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Hyun Goo Kang, None; Nayeong Gu, None; Hyung Keun Lee, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 989. doi:
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      Hyun Goo Kang, Nayeong Gu, Hyung Keun Lee; Lymphatic Hypoplasia Induced in Mice Reduces Recruitment of Immune Cells to the Ocular Surface in Low-grade Chronic Inflammation Such As Dry Eye. Invest. Ophthalmol. Vis. Sci. 2017;58(8):989.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : While normal cornea actively maintains an avascular and alymphatic state, chronic immunoinflammatory disorders such as dry eye(DE) can disrupt the cornea’s immune privilege and promote lymphangiogenesis. This study investigated the effects of lymphangiogenesis in DE by inducing lymphatic hypoplasia using Lyve-1(wt/Cre);VEGFR-2(flox/flox)(△LV) mice.

Methods : DE was induced in both wild type(WT) and △LV mice. Changes in ocular surface, skin, and lymph nodes were noted by tissue staining and volumetric gross measurements. Quantitative fold changes and expression of key factors (IL-4, IL-10, IL-17, VEGF-A/-C/-D, IFN-gamma), markers (Lyve-1, VEGFR-1/-2, podoplanin), and immune cells (CD3, CD4, CD11b, CD19, CD207, CCR7, etc.) on the ocular surface and lymph nodes(LNs) were analyzed by real-time polymerase chain reaction(qPCR) and flow cytometry analysis(FACS).

Results : Tissue staining of Lyve-1 revealed decreased density of lymphatic vessels in LNs and skin of △LV mice, confirmed by fold change in key markers (Lyve-1, podoplanin, VEGFR-2, VEGF-A/-C/-D). The volume of lymph nodes from △LV mice were found to be significantly larger than WT when dry eye was induced (p<0.01). There was an overall increase in lymphocyte concentrations (CD3+, CD11b+, CD19+, and CD45+) on the ocular surface of △LV mice. With DE induction, qPCR fold change of cytokines such as IL-6, IL-10, and IFN-gamma were significantly reduced in △LV mice compared to WT.

Conclusions : Lymphatic hypoplasia appears to compromise induction of adaptive immunity due to diminished homing of APCs. Retention of pro-inflammatory factors due to compromised drainage and reduced recruitment of immunoregulatory factors may lead to additional ocular surface damage.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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