May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Complement Activation by Alternative Pathway is Critical in the Development of Laser–Induced Choroidal Neovascularization
Author Affiliations & Notes
  • P.S. Bora
    Ophthalmology, UAMS, Little Rock, AR
    Ophthalmology, Kentucky Lions Eye Center/ University of Louisville, Louisville, KY
  • S. Kaliappan
    Ophthalmology, UAMS, Little Rock, AR
    Ophthalmology, Kentucky Lions Eye Center/ University of Louisville, Louisville, KY
  • P. Jha
    Ophthalmology, UAMS, Little Rock, AR
    Ophthalmology, Kentucky Lions Eye Center/ University of Louisville, Louisville, KY
  • J.–H. Sohn
    Ophthalmology, Kentucky Lions Eye Center/ University of Louisville, Louisville, KY
  • Q. Xu
    Ophthalmology, UAMS, Little Rock, AR
    Ophthalmology, Kentucky Lions Eye Center/ University of Louisville, Louisville, KY
  • D. Dhaulakhandi
    Ophthalmology, Kentucky Lions Eye Center/ University of Louisville, Louisville, KY
  • H. Kaplan
    Ophthalmology, Kentucky Lions Eye Center/ University of Louisville, Louisville, KY
  • N. Bora
    Ophthalmology, UAMS, Little Rock, AR
    Ophthalmology, Kentucky Lions Eye Center/ University of Louisville, Louisville, KY
  • Footnotes
    Commercial Relationships  P.S. Bora, None; S. Kaliappan, None; P. Jha, None; J. Sohn, None; Q. Xu, None; D. Dhaulakhandi, None; H. Kaplan, None; N. Bora, None.
  • Footnotes
    Support  EY13335, EY014623 HIGHWIRE EXLINK_ID="47:5:4167:1" VALUE="EY014623" TYPEGUESS="GEN" /HIGHWIRE , EY016205 HIGHWIRE EXLINK_ID="47:5:4167:2" VALUE="EY016205" TYPEGUESS="GEN" /HIGHWIRE , R24 EY016636 HIGHWIRE EXLINK_ID="47:5:4167:3" VALUE="EY016636" TYPEGUESS="GEN" /HIGHWIRE , Commonwealth of Kentucky Research Challenge Trust Fund and Research to Prevent Blindness, Inc. NY.
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 4167. doi:
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    • Get Citation

      P.S. Bora, S. Kaliappan, P. Jha, J.–H. Sohn, Q. Xu, D. Dhaulakhandi, H. Kaplan, N. Bora; Complement Activation by Alternative Pathway is Critical in the Development of Laser–Induced Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4167.

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

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Abstract

Purpose: : The purpose of this study was to explore the role of classical, lectin and alternative pathways of complement activation in laser–induced choroidal neovascularization (CNV).

Methods: : CNV was induced by laser photocoagulation in C57BL/6 mouse with krypton red laser. Retinal pigment epithelium (RPE)–choroid–scleral flat mounts prepared from harvested eyes were stained for elastin and the incidence of CNV was determined by confocal microscopy. The size of the CNV complex was graded by morphometric analysis of the images obtained from confocal microscopy. In C57BL/6 mice classical, lectin and alternative pathways were blocked by tail vein injection of siRNA against C1q, C4 and factor B. CNV was also induced in C4–/– and C5 –/– mice. RPE–choroidal–scleral tissues were pooled separately for RT–PCR and Western blot analysis of growth factors.

Results: : C4 –/– mice developed CNV similar to their WT controls and inhibition of C1q by siRNA had no effect on the development of CNV. In contrast, CNV did not develop in C5 –/– mice and C57BL/6 mice treated with factor B siRNA. Inhibition of the alternative pathway by factor B siRNA resulted in decreased levels of angiogenic factors – VEGF and TGF–ß2.

Conclusions: : In conclusion, our results demonstrate that factor B–dependent alternative pathway activation plays a key role in laser–induced CNV in mouse. Thus, specific blockade of alternative pathway may represent a therapeutically relevant strategy to inhibit CNV.

Keywords: age-related macular degeneration • neovascularization • inflammation 
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