病理性眼部血管新生，包含眼角膜血管新生、老年性退化性黃斑部病變、糖尿病視網膜病變、早產兒視網膜病變等，是血管內皮生長因子過度表現所導致，也是造成失明的主要原因。目前治療著重於抗血管內皮生長因子，但復發性血管新生以及全身性副作用仍然是臨床上難以解決的問題，因此目前急需研究與發展不同於傳統抗血管內皮生長因子的治療。我們先前的研究已經發現，重組凝血酶調節素可和Lewis Y抗原結合，抑制血管發炎以及血管生成，然而，凝血酶調節素和血管內皮生長因子誘發病理性血管新生的關聯卻從未被探討過。在本研究中，我們發現重組凝血酶調節素在細胞模式中可以抑制血管內皮生長因子所誘發之血管新生。在高氧誘發視網膜病變動物模式下，重組凝血酶調節素同樣顯著的抑制視網膜血管新生，但並不影響正常生理性血管生成，缺少凝血酶調節素則會加重病理性血管新生。我們同時發現，重組凝血酶調節素除了抑制在上游調控血管內皮生長因子生長之低氧誘導因子-1α，介白質-6和細胞間吸附因子-1等發炎同控因子也會被明顯抑制。我們的研究成果指出，重組凝血酶調節素同時具有抑制血管新生與抑制發炎的雙重效果，未來具有治療病理性眼部血管新生的潛力。

Pathological ocular angiogenesis (POA), including corneal neovascularization, age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity, are major causes of blindness over the world. Current treatments focus on anti-vascular endothelial growth factor (VEGF) therapy, but persistent avascular retina, recurrent intravitreal neovascularization, and general adverse effects are reported. We have previously found that recombinant thrombomodulin domain 1 (rTMD1) interacts with Lewis Y antigen to suppress vascular inflammation and inhibit epidermal growth factor-induced angiogenesis. However, the function of rTMD1 in VEGF-induced POA remains unknown. In this study, we found that rTMD1 inhibits VEGF-induced angiogenesis in vitro. In oxygen induced retinopathy (OIR) animal model, rTMD1 treatment significantly decreased retinal neovascularization but spares normal physiological vessel growths. Furthermore, loss of TMD1 significantly promoted POA in OIR. Meanwhile, hypoxia-inducible factor-1α, the transcription factor located on the upstream of VEGF, was suppressed after rTMD1 treatment. The levels of interleukin-6, and intercellular adhesion molecule-1 were also significantly suppressed. In conclusion, our results suggest that rTMD1 has dual effects to suppress pathological angiogenesis and inflammation in OIR. These data bring forth the possibility of rTMD1 as a novel therapeutic agent for POA.

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