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M. H. Kuehn, A. V. Dumitrescu, R. J. Ryan, Y. H. Kwon; Accumulation of Complement Components in the Glaucomatous Human Optic Nerve. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4319.
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Recent studies by our laboratory have indicated the presence of components of the complement system in the glaucomatous retina. Complement may function, at least in part, to mediate the rapid removal of degenerating retinal ganglion cells (RGC) and their axons. In this study we sought to evaluate the presence of the complement system proteins C1q and C3 and the membrane attack complex (MAC) in the optic nerve (ON) of human donor eyes from patients with and without glaucoma.
Human eyes, from donors with and without glaucoma (N=20), were preserved in 4% paraformaldehyde within 5 hours postmortem. Subsequent medical chart analysis served to identify groups of donors with advanced primary open angle glaucoma (cup to disc ratio 0.6-0.9, and documented visual field deficits and decreased visual acuity) and age-matched controls. Donors with indications of other ocular disease, with the exception of cataracts, were excluded. The optic nerve head and 5-15 mm of ON from these donors were embedded in sucrose and 7 µm cryosections were prepared longitudinally through the ON head, the lamina cribrosa, and the ON. The sections were incubated with antibodies directed against C1q, C3 or MAC, visualized with appropriate secondary antibodies, and counterstained with DAPI. Sections were analyzed by fluorescence microscopy. In addition, RNA was extracted from additional human optic nerves. RNA was reverse transcribed and used for RT-PCR.
As described previously, in eyes obtained from glaucoma donors pronounced staining was detected in the neural retina associated with ganglion cells and the nerve fiber layer. In addition, C1q, C3 and MAC could also be detected in the region of the lamina cribrosa as well as in the postlaminar ON of these donors. In the ON complement labeling appeared to be primarily associated with glial cells. These deposition patterns could be readily observed in all samples derived from donors with glaucoma. In contrast, samples from non-glaucoma eyes displayed sparse or no C1q, C3, and MAC labeling. RT-PCR analysis detected the presence of C1qa and C3 transcripts within the optic nerve, suggesting that the observed complement components are, at least in part, synthesized locally.
The optic nerve and the lamina cribrosa of patients with advanced POAG display markedly enhanced deposition of several components of the complement cascade. Our findings agree with recent reports demonstrating an important role of MAC in Wallerian degeneration of neuronal axons and further support a functional role of the complement system in the neuroinflammatory processes that accompany glaucomatous retinal degeneration.
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