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Tatiana Ecoiffier, Inho Choi, Young Hong, Sunju Lee, Lu Chen; 9-cis Retinoic Acid Modulates Corneal Lymphangiogenesis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6388.
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© ARVO (1962-2015); The Authors (2016-present)
9-cis retinoic acid (RA) is a metabolite of vitamin A and controls many biological and pathological processes. The purpose of this study is to use the unique tissue of the cornea to investigate potential roles of 9-cis RA in hemangiogenesis (HG; the development of new blood vessels), lymphangiogenesis (LG; the development of new lymphatic vessels), or both, which remain largely unknown to this stage.
Uniform slow-release 9-cis RA or control pellets were implanted in normal adult BALB/c mouse corneas. Flat-mount corneas were harvested at Day 14 after the surgeries for immunofluorescent microscopic studies using specific antibodies against CD31 (a panendothelial cell marker) and LYVE-1 (a lymphatic marker). Digital images were analyzed by NIH Image J software. In addition, corneal HG was also evaluated by ophthalmic slit-lamp examinations.
As evaluated by the percentage of covered area, 9-cis RA triggered a significant in-growth of lymphatic vessels into the cornea (P = 0.005, n = 10). However, no statistical significance was detected in blood vessel development.
This study provides the first evidence showing that 9-cis RA promotes LG in the cornea. Our data also demonstrate that in response to a certain pathological stimulation, corneal LG and HG can behave differently or independently. Further studies on this molecule may provide new mechanisms underlying differential processes of LG and HG and the development of novel strategies to treat lymphatic-related diseases, such as transplant rejection, cancer metastasis, inflammation, and lymphedema.
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