关键词: CD55 Complementary system Inflammation Myopia Retina decay-accelerating factor (DAF)

Mesh : Adolescent Animals Female Humans Male Young Adult CD55 Antigens / metabolism Complement Activation / drug effects Complement C3 / metabolism Conjunctivitis, Allergic / immunology metabolism Cytokines / metabolism Disease Models, Animal Inflammation Myopia / metabolism Tears / metabolism Tumor Necrosis Factor-alpha / metabolism Complement C5 / metabolism

来  源:   DOI:10.1016/j.molimm.2024.05.005

Abstract:
Myopia is regarded as a worldwide epidemic ocular disease, has been proved related to inflammation. CD55, also known as decay-accelerating factor (DAF) can modulate the activation of complement through inhibiting the formation of complement 3 convertase and its dysregulation is involved in various inflammatory diseases. To investigate the association between CD55 and myopia, and to test whether CD55 can inhibit myopia development by suppressing inflammation in the eye, we use three different animal models including monocular form-deprivation myopia, myopia induced by TNF-α administration and allergic conjunctivitis animal model to reveal the CD55 in myopia development. The tears of thirty-eight participants with different spherical equivalents were collected and CD55 in the tears were also analyzed. Complement 3 and complement 5 levels increased while CD55 levels decreased in allergic conjunctivitis and myopic eyes. After anti-inflammatory drugs administration, CD55 expression was increased in monocular form-deprivation myopia model. We also found inflammatory cytokines TGF-β, IL-6, TNF-α, and IL-1β may enhance complement 3 and complement 5 activation while CD55 level was suppressed contrary. Moreover, lower CD55 levels were found in the tears of patients with myopia with decreased diopter values. Finally, CD55-Fc administration on the eyelids can inhibit the elongation of axial length and change of refractive error. CD55-Fc application also suppress myopia development subsequent to complement 3 and complement 5 reduction and can lower myopia-specific (MMP-2 and TGF-β) cytokine expression in TNF-α induced myopia animal model. This suggests that CD55 can inhibit myopia development by suppression of complement activation and eventual down-regulation of inflammation.
摘要:
近视被认为是一种世界性的流行性眼病,已被证明与炎症有关。CD55,也称为衰变加速因子(DAF),可以通过抑制补体3转化酶的形成来调节补体的激活,其失调与各种炎性疾病有关。探讨CD55与近视的关系,并测试CD55是否可以通过抑制眼部炎症来抑制近视发展,我们使用三种不同的动物模型,包括单眼形觉剥夺性近视,TNF-α诱导的近视和过敏性结膜炎动物模型揭示了CD55在近视发展中的作用。收集具有不同球形当量的38名参与者的眼泪,并分析眼泪中的CD55。过敏性结膜炎和近视眼中补体3和补体5水平升高,而CD55水平降低。服用抗炎药后,CD55在单眼形觉剥夺性近视模型中表达增加。我们还发现了炎症细胞因子TGF-β,IL-6,TNF-α,IL-1β可以增强补体3和补体5的激活,而CD55水平则相反。此外,在屈光度值降低的近视患者的泪液中发现较低的CD55水平。最后,在眼睑上施用CD55-Fc可抑制眼轴长度的延长和屈光不正的改变。CD55-Fc应用还抑制补体3和补体5减少后的近视发展,并且可以降低TNF-α诱导的近视动物模型中的近视特异性(MMP-2和TGF-β)细胞因子表达。这表明CD55可以通过抑制补体激活和最终下调炎症来抑制近视发展。
公众号