Purchase this article with an account.
Huihui Chen, Kin-Sang Cho, Xuanchu Duan, Dongfeng Chen; Autoimmunity Contributes To The Mechanism Of Optic Nerve Degeneration And Rgc Neuropathy Following Elevation Of Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2422.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
glaucoma is the leading cause of unconvertible blindness in the world, and the intraocular pressure (IOP) is still the only target in clinical therapy. However, in numbers of patients, retinal ganglion cells (RGC) and their axons continue to degenerate even when IOP is under a perfect control. Here, we investigate the contribution of autoimmune responses to axon and RGC degeneration in glaucoma using mice deficient for T and B cell function and a microbead-induced model of ocular hypertension.
Elevation of IOP was induced unilaterally in adult wild-type (C57BL/6J) mice and mice deficient for T cell and B cell functions (Rag1-/-) by injecting 15µm polystyrene microbeads to the anterior chamber. Mouse IOPs were monitored every other day using a TonoLab. At 2 to 8 weeks after microbead injection, the degrees of RGC and axon degeneration were assessed quantitatively using electron microscopy and immunohistochemistry with a primary antibody against an RGC specific marker. T cell infiltration and complement deposition were evaluated in retinal flat-mount by immunohistochemistry. To further investigate the roles of T cell-mediated responses in glaucomatous RGC and axon degeneration, CD4+ T cells isolated from C57BL/6J wild-type mice that were induced to develop high IOP were adoptively transferred to Rag1-/- mice. The degrees of RGC and axon degeneration were quantified as described above.
All mice that received anterior chamber injection of microbeads exhibited transient IOP elevation for approximately 3 weeks. Rag1-/- mice exhibited significant less axon and RGC loss than that of C57BL/6J mice at both 2 and 8 weeks post injection of microbeads. Infiltration of T cells and compliment deposition were detected in retinas of wild-type, but not Rag1-/-, mice at 2-3 weeks after the elevation of IOP. Adoptive transfer of CD4+ T cells isolated from high IOP C57BL/6J mice significantly facilitated the axon and RGC degeneration in Rag1-/- mice as compared to Rag1-/- mice received cell transfer from the normal IOP group.
Elevation of IOP in mice triggers adaptive immune responses that attack RGC and axons and contribute to glaucomatous neurodegeneration. .
This PDF is available to Subscribers Only