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Qiong Ding, Alina V. Dumitrescu, Amy C. Cook, Susan M. Bushek, Markus H. Kuehn; Lack Of Immunoglobulins Does Not Prevent C1q Binding To RGC And Does Not Alter The Progression Of Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4603.
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We previously reported deposition of complement components 1q (C1q) and 3 (C3) in association with retinal ganglion cells (RGC) in the glaucomatous retina. C1q is not known to bind directly to cells, relying instead on adapter molecules. Traditionally these were assumed to be immunoglobulins (Ig) but it has now become clear that a number of molecules can fulfill this role. The purpose of this study was to evaluate whether C1q binding and activation of the complement cascade in the glaucomatous retina is dependent upon the presence of Ig.
Experimental glaucoma was induced in C57BL/6J and B6.129S7-Rag1tm1Mom/J (RAG1-/-) mice using the microbead occlusion model (N=20/group). Damage to the optic nerve as well as the fraction of surviving RGC were determined using an established grading scheme and through counting of gamma synuclein positive cells in whole mounted retinas, respectively. Binding of C1q and C3 to the RGC was visualized using immunohistochemistry of retinal cryosections. Complement activation was also evaluated in vitro using dissociated retinal cell cultures.
Injection of microbeads into the anterior chamber of mice induces mild IOP elevation in the majority of treated eyes (average = 4.9 mmHg above baseline). Elevated intraocular pressure was maintained for up to 4 weeks. This experimental glaucoma results in RGC loss, progressive optic nerve damage, and concomitant C1q binding to RGC in both normal and RAG1 -/- mice. The absence of Ig does not affect the rate of axonal damage or RGC loss (p=0.39 and 0.12 after 2 and 4 weeks, respectively). C1q and C3 immunoreactivity associated with RGC was observed both in normal and RAG1-/- mice. RGC in retinal cultures maintained in serum-free media are also C1q immunoreactive, demonstrating that Ig is not required for C1q binding to damaged RGC.
Our data demonstrate that lack of immunoglobulins and mature T/B cells does not influence the progression of glaucoma. Furthermore, immunoglobulins do not appear to be required for C1q binding and complement cascade activation on damaged RGC. These findings suggest that C1q recognizes an alternative binding partner expressed by stressed RGC.
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