RETINA AND RETINAL-PIGMENT EPITHELIAL-CELL AUTOANTIBODIES ARE PRODUCED DURING MURINE CORONAVIRUS RETINOPATHY

The murine coronavirus, mouse hepatitis virus (MHV), JHM strain, induc es 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 asso ciated with the presence of virus particles. In the late phase of the disease, day 10 to 140, a retinal degeneration is observed and is asso ciated with the absence of both virus particles and inflammatory cells . We show that the retinal degenerative process is also associated wit h the presence of antiretinal autoantibodies. In total, 22 of 23 sera collected from 10 to 70 days after JHM virus inoculation contained ant iretinal autoantibodies. These autoantibodies are not found in sera fr om normal or mock-injected mice. Antibodies to retinal tissue were ide ntified as two distinct patterns of immunoperoxidase staining on froze n sections of normal rat eyes, retinal autoantibodies and retinal pigm ent epithelium (RPE) autoantibodies. The antiretinal autoantibodies fi rst appeared as IgM class antibodies that shifted to IgG class autoant ibodies. The anti-RPE cell autoantibodies were predominantly of the Ig G class. Sera that were positive for these autoantibodies did not stai n with liver or kidney sections but 2 of 3 did react with rat brain se ctions. 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 pr oduced. However, just as is noted in the BALB/c mice, antivirus neutra lizing antibodies are produced in the infected CD-1 mice. These findin gs suggest a role for autoimmunity in the pathogenesis of murine coron avirus induced retinal degeneration. This study establishes an animal model for the study of humoral autoimmune responses in human retinal d egenerations.