May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Complement Activation Accelerates Retinal Ganglion Cell Loss in Ocular Ischemia
Author Affiliations & Notes
  • M. H. Kuehn
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa
  • C. Y. Kim
    Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea
  • B. Jiang
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa
  • Y. H. Kwon
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa
  • Footnotes
    Commercial Relationships M.H. Kuehn, None; C.Y. Kim, None; B. Jiang, None; Y.H. Kwon, None.
  • Footnotes
    Support Unrestricted Grant to the Department of Ophthalmology from Research to Prevent Blindness and an unrestricted Glaucoma Educational Grant from Allergan
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 4199. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      M. H. Kuehn, C. Y. Kim, B. Jiang, Y. H. Kwon; Complement Activation Accelerates Retinal Ganglion Cell Loss in Ocular Ischemia. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4199.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose:: Inappropriate activation of the complement cascade contributes to neuronal loss in several neurodegenerative diseases. In the eye, complement components accumulate specifically in association with retinal ganglion cells (RGC) in human eyes with glaucoma and in animal models of ocular hypertension and ischemia. Expression of complement may support degradation and phagocytocis of damaged RGC, but activation of the complement cascade has the potential to exacerbate RGC loss either directly through the formation of the membrane attack complex or secondarily through the activation of retinal glial elements. This study was designed to evaluate if mice with a disrupted complement cascade exhibit altered retinal pathophysiology following retinal ischemia.

Methods:: RRetinal ischemia was induced through hydrostatic elevation of intraocular pressure in wild-type and complement component 3 (C3-/-) knockout mice (N=30 per group). Eyes were harvested 7 and 21 days after induction and optic nerve axon degeneration was evaluated histologically to estimate RGC loss. Complement gene expression was evaluated by quantitative PCR. The deposition of C3 (wild-type animals only) and complement component 1q (C1q) was confirmed using immunohistochemistry.

Results:: Retinal ischemia resulted in deposition of C1q in all evaluated animals. As expected, C3 accumulation only occurred in wild-type mice. 7 days after induction optic nerves of C3-/- animals revealed mild damage while wild type mice displayed significant damage at that time. Axonal damage in wild type animals increased slightly between 7 and 21 days. In contrast, axonal damage in C3-/- animals continued at a more rapid pace. Thus 21 days after ischemia differences between the two groups were less pronounced although C3-/- animals continued to display less axonal damage than wild type animals.

Conclusions:: Our findings demonstrate that components of the complement cascade are actively involved in the pathophysiology of retinal ischemia. In normal animals the majority of ganglion cell damage occurs within a few days after the ischemic insult and damage increases only slightly thereafter. In contrast, C3-/- display a more gradual loss of optic nerve axons. These data indicate that components of the complement cascade are involved in the rapid degeneration and perhaps removal of injured RGC. Furthermore, differences in the number of surviving RGC persist three weeks after the ischemic insult suggesting that a fraction of healthy RGC may be damaged through the activities of the complement cascade.

Keywords: ischemia • ganglion cells • retinal degenerations: cell biology 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.