Disruption of the complement cascade delays retinal ganglion cell death following retinal ischemia-reperfusion

Markus H. Kuehn, chanyun kim, Bing Jiang, Alina V. Dumitrescu, Young H. Kwon

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)89-95
Number of pages7
JournalExperimental Eye Research
Volume87
Issue number2
DOIs
Publication statusPublished - 2008 Aug 1

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Retinal Ganglion Cells
Reperfusion
Cell Death
Ischemia
Optic Nerve
Retina
Retinal Degeneration
Complement C3
Complement Activation
Reperfusion Injury
Phagocytosis
Neurodegenerative Diseases
Glaucoma
Axons
Cell Survival
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Kuehn, Markus H. ; kim, chanyun ; Jiang, Bing ; Dumitrescu, Alina V. ; Kwon, Young H. / Disruption of the complement cascade delays retinal ganglion cell death following retinal ischemia-reperfusion. In: Experimental Eye Research. 2008 ; Vol. 87, No. 2. pp. 89-95.
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Disruption of the complement cascade delays retinal ganglion cell death following retinal ischemia-reperfusion. / Kuehn, Markus H.; kim, chanyun; Jiang, Bing; Dumitrescu, Alina V.; Kwon, Young H.

In: Experimental Eye Research, Vol. 87, No. 2, 01.08.2008, p. 89-95.

Research output: Contribution to journalArticle

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