Autoimmunity Contributes To The Mechanism Of Optic Nerve Degeneration And RGC Neuropathy Following Elevation Of Intraocular Pressure

Purpose:glaucoma is the leading unconvertible blindness disease in the world, and the intraocular pressure (IOP) is still the only main target in the clinical therapy. However, the axon and retinal ganglion cell (RGC) will keep losing without IOP elevation the in quiet number of patients. Our study is tried to investigate the autoimmune response might also contribute to the axon and RGC death other than the elevation of IOP, and hsp27 might be a new clinical therapy target of glaucoma patients.Methods:Elevation of IOP was induced unilaterally in adult C57BL/6J, BCKO, TCKO and Rag1-/-mice by injecting polystyrene microbeads to the anterior chamber. After elevated IOP for 2, and 8 weeks, the degree of RGC and axon degeneration was assessed quantitatively using electron microscopy and immunohistochemistry. The T cell, deposited complement Elispot to the Hsp27 and antibody concentration in serum are detected in the glaucoma B6 mice and DBA2/J mice. Then we adaptive transfer the CD4+T cell from hsp27 immuned mice to the glaucoma B6 mice, and then detect the axon and RGC loss.Results:24 mice that received anterior chamber injection of microbeads exhibited transient IOP elevation for about 3 weeks. Rag1-/-TCKO and BCKO, mice exhibited significant axon survive than the B6 mice. T cell infiltrated into the glaucoma retina of B6 and DBA2/J mice were detected during elevation of IOP. Compliment deposit also was detected even after IOP come back to normal. Elispot shows that the elevation of IOP can stimulate the immune response to hsp27. When adaptive transfer the CD4+T cell from the hsp27 immuned mice, the glaucoma B6 mice significant increased both RGC bodies and their axons degenerated.Conclusions:elevation of IOP in mice can trigger immune responses to retina antigens. These immune response will injury against RGC and axon, however retina pathology is reduced in mice lacking T cells and B cells. Hsp27 might be the potential antigen which against the RGC and axon in B6 mice. Hsp27 can be the injury marker and potential target in clinical glaucoma treatment.