Recent reports have indicated that components of the complement cascade are synthesized during the degeneration of retinal ganglion cells (RGC) in glaucoma. While complement deposition in the retina may simply serve to aid phagocytosis of damaged RGC, activation of the complement cascade can also contribute to neuronal loss in neurodegenerative diseases. This study was designed to determine if disruption of the complement cascade affects RGC survival in a murine model of retinal ischemia-reperfusion (I/R) injury. We induced retinal ischemia in the eyes of normal mice and mice with a targeted disruption of the complement component 3 (C3) gene. Tissue was harvested 7 and 21 days after induction of I/R and retinal complement synthesis was determined by quantitative PCR and immunohistochemical methods. RGC death and associated axon loss was evaluated through histological examination of the optic nerve and retina. Our data show that retinal I/R induces the expression and deposition of complement components. C3 deficient mice clearly exhibited reduced optic nerve damage and substantial preservation of RGC 1 week after I/R when compared to normal animals (p = 0.005). Three weeks after the ischemic event C3 deficient mice retained more RGC cell bodies although the degree of optic nerve damage was similar between both groups. These findings demonstrate that inhibition of the complement cascade delays optic nerve axonal and RGC degeneration in retinal I/R. It appears that injured RGC are targeted and actively destroyed through complement mediated processes. These results may have implications for the pathophysiology and clinical management of ischemic retinal conditions.
Bibliographical noteFunding Information:
The authors would like to thank Dr Michael Anderson for his help in the evaluation of the optic nerves, Dr Robert Mullins for help with immunohistochemical methods and Paul Abrams, Jared Vincenti and Adam Hedberg-Buenz for technical assistance. This work was supported by an unrestricted grant from Research to Prevent Blindness to the UI Department of Ophthalmology, an Unrestricted Glaucoma Educational Grant from Allergan (CYK), and the Charles D. Phelps Memorial Endowment (BJ and AVD).
All Science Journal Classification (ASJC) codes
- Sensory Systems
- Cellular and Molecular Neuroscience