Sublytic Membrane-Attack-Complex Activation and VEGF Secretion in Retinal Pigment Epithelial Cells

  • Kannan Kunchithapautham
  • Mausumi Bandyopadhyay
  • Mohammad Dahrouj
  • Joshua M. Thurman
  • Bärbel RohrerEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)


Uncontrolled activation of the alternative complement pathway and secretion of vascular endothelial growth factor (VEGF) are thought to be associated with age-related macular degeneration (AMD). Previously, we have shown that in RPE monolayers, oxidative stress induced by H2O2 exposure reduced complement inhibition on the cell surface. The resulting increased level of sublytic complement activation resulted in VEGF release, which disrupted the barrier facility of these cells as determined by transepithelial resistance (TER) measurements. Here, we have asked whether other environmental factors known to be associated with AMD, such as A2E, iron, and smoking, similarly sensitize the RPE to complement attack. Exposure of RPE monolayers with stable TER to A2E, ferric ammonium citrate (FAC), and smoke-extract at pathological concentrations resulted in significant increase in oxidative stress as determined by reactive oxygen species and superoxide measurements. However, an additional challenge with normal human serum only resulted in a decrease in TER in H2O2-exposed cells as reported previously, whereas A2E-, FAC-, and smoke-extract-treated cells were unaffected. Effects on TER were directly correlated with the release of VEGF. Taken together, identifying which AMD-associated stimuli result in sublytic MAC induction of VEGF secretion might offer novel opportunities to selectively inhibit pathological VEGF release.


RPE monolayer VEGF Complement system Sublytic activation Age-related macular degeneration Transepithelial resistance 



This work was supported in part by National Institutes of Health Grants DK077661 and DK076690 (JMT), the Foundation Fighting Blindness (BR), and an unrestricted grant to MUSC from Research to Prevent Blindness, Inc., New York, NY. BR is a Research to Prevent Blindness Olga Keith Wiess Scholar. The authors declare the following disclosures. JMT and BR are consultants for Taligen Therapeutics, Inc. The authors thank Luanna Bartholomew for editorial assistance.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Kannan Kunchithapautham
    • 1
  • Mausumi Bandyopadhyay
    • 2
  • Mohammad Dahrouj
    • 2
  • Joshua M. Thurman
    • 3
  • Bärbel Rohrer
    • 4
    Email author
  1. 1.Department of Neurosciences, Division of ResearchMedical University of South CarolinaCharlestonUSA
  2. 2.Department of OphthalmologyMedical University of South CarolinaCharlestonUSA
  3. 3.Department of Medicine, Denver School of MedicineUniversity of ColoradoDenverUSA
  4. 4.Departments of Ophthalmology and Neurosciences, Division of ResearchMedical University of South CarolinaCharlestonUSA

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