Hooks J J, Percopo C, Wang Y, Detrick B
Immunology and Virology Section, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1993 Sep 15;151(6):3381-9.
The murine coronavirus, mouse hepatitis virus (MHV), JHM strain, induces a biphasic retinal disease in adult BALB/c mice. In the early phase of the disease, day 1 to 7, a retinal vasculitis is noted and is associated with the presence of virus particles. In the late phase of the disease, day 10 to 140, a retinal degeneration is observed and is associated with the absence of both virus particles and inflammatory cells. We show that the retinal degenerative process is also associated with the presence of antiretinal autoantibodies. In total, 22 of 23 sera collected from 10 to 70 days after JHM virus inoculation contained antiretinal autoantibodies. These autoantibodies are not found in sera from normal or mock-injected mice. Antibodies to retinal tissue were identified as two distinct patterns of immunoperoxidase staining on frozen sections of normal rat eyes, retinal autoantibodies and retinal pigment epithelium (RPE) autoantibodies. The antiretinal autoantibodies first appeared as IgM class antibodies that shifted to IgG class autoantibodies. The anti-RPE cell autoantibodies were predominantly of the IgG class. Sera that were positive for these autoantibodies did not stain with liver or kidney sections but 2 of 3 did react with rat brain sections. A second mouse strain, CD-1, was also evaluated because these animals respond to JHM virus inoculation by developing only the early phase of this disease, i.e. vasculitis. On day 10 postinoculation, the retina architecture has a normal appearance. In these mice, which are free of a retinal degeneration, antiretinal autoantibodies are not produced. However, just as is noted in the BALB/c mice, antivirus neutralizing antibodies are produced in the infected CD-1 mice. These findings suggest a role for autoimmunity in the pathogenesis of murine coronavirus induced retinal degeneration. This study establishes an animal model for the study of humoral autoimmune responses in human retinal degenerations.
鼠冠状病毒，即小鼠肝炎病毒（MHV）JHM株，可在成年BALB/c小鼠中诱发双相视网膜疾病。在疾病早期，即第1至7天，可见视网膜血管炎，且与病毒颗粒的存在有关。在疾病晚期，即第10至140天，观察到视网膜变性，且与病毒颗粒和炎性细胞的缺失有关。我们发现，视网膜变性过程还与抗视网膜自身抗体的存在有关。在接种JHM病毒后10至70天收集的23份血清中，共有22份含有抗视网膜自身抗体。正常或假注射小鼠的血清中未发现这些自身抗体。在正常大鼠眼睛的冰冻切片上，视网膜组织抗体表现为免疫过氧化物酶染色的两种不同模式，即视网膜自身抗体和视网膜色素上皮（RPE）自身抗体。抗视网膜自身抗体最初表现为IgM类抗体，随后转变为IgG类自身抗体。抗RPE细胞自身抗体主要为IgG类。这些自身抗体呈阳性的血清在肝脏或肾脏切片上不着色，但3份中有2份与大鼠脑切片发生反应。还对第二种小鼠品系CD-1进行了评估，因为这些动物接种JHM病毒后仅出现该疾病的早期阶段，即血管炎。接种后第10天，视网膜结构外观正常。在这些未发生视网膜变性的小鼠中，未产生抗视网膜自身抗体。然而，正如在BALB/c小鼠中所观察到的，感染的CD-1小鼠会产生抗病毒中和抗体。这些发现表明自身免疫在鼠冠状病毒诱导的视网膜变性发病机制中起作用。本研究建立了一个用于研究人类视网膜变性中体液自身免疫反应的动物模型。
