Mast cells are classically thought to play an important role in protection against helminth infections and in the induction of allergic diseases; however, recent studies indicate that these cells also contribute to neovascularization, which is critical for tissue remodeling, chronic inflammation, and carcinogenesis. Here, we demonstrate that mast cells are essential for sprouting angiogenesis in a murine model of oxygen-induced retinopathy (OIR). Although mouse strains lacking mast cells did not exhibit retinal neovascularization following hypoxia, these mice developed OIR following infusion of mast cells or after injection of mast cell tryptase (MCT). Relative hypoxia stimulated mast cell degranulation via transient receptor potential ankyrin 1. Subsequent surges in MCT stimulated retinal endothelial cells to produce monocyte chemotactic protein-1 (MCP1) and angiogenic factors, leading to sprouting angiogenesis. Mast cell stabilizers as well as specific tryptase and MCP1 inhibitors prevented the development of OIR in WT mice. Preterm infants with early retinopathy of prematurity had markedly higher plasma MCT levels than age-matched infants without disease, suggesting mast cells contribute to human disease. Together, these results suggest therapies that suppress mast cell activity should be further explored as a potential option for preventing eye diseases and subsequent blindness induced by neovascularization.

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肥大细胞过度活动支持氧诱导的视网膜病变的发展

传统上认为肥大细胞在预防蠕虫感染和诱导过敏性疾病中起重要作用。然而，最近的研究表明，这些细胞也有助于新血管形成，这对于组织重塑，慢性炎症和致癌作用至关重要。在这里，我们证明肥大细胞对于在氧诱导性视网膜病（OIR）的鼠模型中萌发血管生成必不可少。尽管缺乏肥大细胞的小鼠品系在缺氧后未显示视网膜新血管形成，但这些小鼠在注入肥大细胞或注射肥大细胞类胰蛋白酶（MCT）后出现OIR。相对缺氧通过瞬时受体电位锚蛋白1刺激肥大细胞脱粒。随后的MCT激增刺激视网膜内皮细胞产生单核细胞趋化蛋白-1（MCP1）和血管生成因子，从而导致发芽的血管生成。肥大细胞稳定剂以及特定的类胰蛋白酶和MCP1抑制剂阻止了WT小鼠OIR的发展。早产儿早期视网膜病变早产儿的血浆MCT水平明显高于无疾病的年龄匹配婴儿，表明肥大细胞是人类疾病的原因。总之，这些结果表明，应进一步探索抑制肥大细胞活性的疗法，作为预防由新血管形成引起的眼部疾病和随后的失明的潜在选择。肥大细胞稳定剂以及特定的类胰蛋白酶和MCP1抑制剂阻止了WT小鼠OIR的发展。早产儿早期视网膜病变早产儿的血浆MCT水平明显高于无疾病的年龄匹配婴儿，表明肥大细胞是人类疾病的原因。总之，这些结果表明，应进一步探索抑制肥大细胞活性的疗法，作为预防由新血管形成引起的眼部疾病和随后的失明的潜在选择。肥大细胞稳定剂以及特定的类胰蛋白酶和MCP1抑制剂阻止了WT小鼠OIR的发展。早产儿早期视网膜病变早产儿的血浆MCT水平明显高于无疾病的年龄匹配婴儿，表明肥大细胞是人类疾病的原因。总之，这些结果表明，应进一步探索抑制肥大细胞活性的疗法，作为预防由新血管形成引起的眼部疾病和随后的失明的潜在选择。