Lack of lymphatics and lymph node-mediated immunity in choroidal neovascularization

Shintaro Nakao, Souska Zandi, Ri ichiro Kohno, Dawei Sun, Takahito Nakama, Keijiro Ishikawa, Shigeo Yoshida, Hiroshi Enaida, Tatsuro Ishibashi, Ali Hafezi-Moghadam

研究成果: ジャーナルへの寄稿学術誌査読

7 被引用数 (Scopus)

抄録

Purpose. Inflammation and immune cells regulate choroidal neovascularization (CNV) and could become therapeutic targets in age-related macular degeneration (AMD). Lymphangio-genesis is a key component of various inflammatory diseases. Whether lymphangiogenesis and lymph node-mediated immunity are involved in the pathogenesis of AMD is not understood. Methods. To investigate lymphangiogenesis in CNV, we generated CNV in animals by laser and studied surgically removed CNV membranes from uveitis and AMD patients. Immunohisto-chemistry was performed with lymphatic vessel endothelial hyaluronate receptor 1 (LYVE-1) and podoplanin antibodies. VEGF-C and VEGFR-3 expressions were examined with immunohistochemistry and Western blotting. To examine the role of lymph node in CNV, we lasered lymphotoxin alpha-deficient mice (LTα-/-) and measured the CNV volume. Results. Immunohistochemistry showed that LYVE-1(+) macrophages infiltrated in acutely induced CNV although lymphatic tubes did not form. CNV membranes from patients did not show LYVE-1(+)podoplanin(+) vessels, suggesting the lack of lymphangiogenesis in AMD and uveitis. Western blots and immunostaining revealed VEGF-C and VEGFR-3 expression in CNV lesions, mainly in macrophages and angiogenic endothelial cells. Using fluorescent microsphere tracers, we show a path for cellular migration from the eye to the cervical lymph nodes (LNs) during CNV. However, CNV injury did not cause LN swelling. CNV volume did not differ between wild-type and LN-deficient mice, suggesting that LN is not a key component of early CNV formation. Conclusions. Laser-induced CNV is not primarily dependent on acquired immunity, nor does the fundus injury affect peripheral LNs. Our results reveal a previously unknown cellular connection between the ocular fundus and the cervical LNs. This connection that in function resembles lymphatics is actively utilized in CNV.

本文言語英語
ページ(範囲)3830-3836
ページ数7
ジャーナルInvestigative Ophthalmology and Visual Science
54
6
DOI
出版ステータス出版済み - 2013

!!!All Science Journal Classification (ASJC) codes

  • 眼科学
  • 感覚系
  • 細胞および分子神経科学

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