The role of the classical complement cascade in synapse loss during development and glaucoma.
Glaucoma is one of the leading causes of vision loss worldwide, yet the signals that initiate the progressive degeneration of optic nerve axons and the selective loss of retinal ganglion neurons (RGCs) remain elusive. Reactive gliosis, release of inflammatory cytokines, and complement upregulation all occur in the early stages of glaucoma in several disease models. Recent work has implicated the classical complement cascade in the elimination of excess synaptic connections in the developing visual system and in early synapse loss associated with glaucoma, suggesting that mechanisms of developmental synapse elimination may be aberrantly re-activated in glaucoma. This review describes current evidence in support of this "synaptic" hypothesis and places complement in the context of other well-described mechanisms of neurodegeneration occurring in the glaucomatous eye.
Rosen
Allison M
AM
F.M. Kirby Neurobiology Center, Children's Hospital Boston and Depart of Neurology, Harvard Medical School, Boston, MA 02115, USA.
Stevens
Beth
B
D000818:Animals; D016923:Cell Death; D003171:Complement Pathway, Classical; D004195:Disease Models, Animal; D005901:Glaucoma / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D051379:Mice; D008959:Models, Neurological; D009410:Nerve Degeneration / Q000276:immunology / Q000473:pathology; D009457:Neuroglia / Q000276:immunology / Q000473:pathology; D015213:Neuroimmunomodulation; D012160:Retina / Q000254:growth & development; D012165:Retinal Ganglion Cells / Q000276:immunology / Q000473:pathology; D012307:Risk Factors; D015398:Signal Transduction; D013569:Synapses / Q000276:immunology* / Q000473:pathology*