Eliminating complement factor D reduces photoreceptor susceptibility to light-induced damage

Bärbel Rohrer, Yao Guo, Kannan Kunchithapautham, Gary S. Gilkeson

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

PURPOSE. Genetic risk factors such as variations in complement factors H (CFH) and B (CFB) have been implicated in the etiology of age-related macular degeneration. It has been hypothesized that inadequate control of complement-driven inflammation may be a major factor in disease pathogenesis. The authors tested the involvement of the complement system in an experimental model for oxidative stress-mediated photoreceptor degeneration, the light-damage mouse model. METHODS. Changes in gene expression were assessed in BALB/c retinas in response to constant-light (CL) exposure using microarrays and real-time PCR. Susceptibility to CL exposure was tested in CFD-/- mice on a BALB/c background. Eyes were analyzed using electrophysiologic and histologic techniques. RESULTS. Genes encoding for proteins involved in complement activation were significantly upregulated after CL. The altered gene profiles were similar to proteins accumulated in drusen and to genes identified in the retina and RPE/choroid of patients with age-related macular degeneration. Cyclic-light reared CFD-/- and CFD+/+ mice had indistinguishable rod function and number; however, after CL challenge, CFD -/- photoreceptors were significantly protected. CONCLUSIONS. These results suggest that rod degeneration in the CL-damaged retina involves the activity of the alternative complement pathway and that eliminating the alternative pathway is neuroprotective. Thus, the light damage albino mouse model may be a good model to study complement-mediated photoreceptor degeneration.

Original languageEnglish (US)
Pages (from-to)5282-5289
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume48
Issue number11
DOIs
StatePublished - Nov 2007

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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