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목적 : While normal cornea actively maintains an avascular and alymphatic state, chronic immunoinflammatory ocular surface 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 disease by inducing lymphatic hypoplasia using Lyve-1(wt/Cre);VEGFR-2(flox/flox)(△LV) mice.
방법 : DE was induced in both wild type (WT) and △LV mice. Degree of corneal erosion in each eye was graded. 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).
결과 : Tissue staining of Lyve-1 revealed decreased density of lymphatic vessels in LNs and skin of △LV, confirmed by fold change in key markers (Lyve-1, podoplanin, VEGFR-2, VEGF-A/-C/-D). There was an increase in lymphocyte concentrations (CD3+, CD11b+, CD19+, and CD45+) on the ocular surface of △LV. With DE induction, qPCR fold change in cytokines such as IL-6, IL-10, and IFN-gamma were significantly reduced in △LV compared to WT mice. Additionally, changes in CCR7+ and CD207+ cells (WT 5.4% vs △LV 1.8%, 2.0% vs 3.9%, respectively) were noted. Expression of IL-7 was increased in △LV mice.
결론 : 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.
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