Neuroinflammation in Glaucoma

Complement Activation in Glaucoma

Glaucoma is characterized morphologically by retinal ganglion cell (RGC) death, degeneration of optic nerve axons, excavation of the optic nerve head, and degeneration of the lateral geniculate nucleus. While the changes in the optic nerve head are the clinical hallmark of glaucoma, it is the loss of RGC that is the ultimate cause of vision loss.

The degeneration of RGC in glaucoma is accompanied by a neuroinflammatory response, involving both retinal glia and RGC. As part of this response retinal cells synthesize components of the complement cascade and complement becomes fixed on RGC and their axons. Notably, we have demonstrated the presence of the cytolytic membrane attack complex in association with RGC both in animal models and in human disease. Deposition of complement on the surface of damaged or dying neurons has been observed in many neurodegenerative diseases and appears to support rapid phagocytosis of apoptotic debris and avoidance of an autoimmune response. Complement activation also engenders the release of the anaphylatoxins C3a and C5a. Receptors for both molecules are present on retinal glial cells and it is likely that complement activation modulates their behavior.

Our studies have also shown that deactivation of the complement cascade in an ischemic mouse model significantly delays axon and RGC degeneration. These findings are in accordance with those by others that demonstrate that the membrane attack complex is essential for rapid Wallerian degeneration. These data suggest that complement not only serves to facilitate uptake of debris of apoptotic RGC, but is actively involved in the destruction damaged RGC and their axons.

Suspected role of the complement cascade in the glaucoma retina

Neuroinflammation is a necessary response of neuronal tissue to injury. Our current studies are designed to understand if this response can be modulated with the aim to lessen RGC loss.