April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Myd88 as a therapeutic target for choroidal neovascularization
Author Affiliations & Notes
  • Nagaraj Kerur
    Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY
  • Younghee Kim
    Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY
  • Yoshio Hirano
    Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY
    Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Japan
  • Valeria Tarallo
    Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY
    Angiogenesis Lab, Institute of Genetics and Biophysics, CNR, Naples, Italy
  • Ana Bastos-Carvalho
    Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY
  • Benjamin Fowler
    Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY
  • Tetsuhiro Yasuma
    Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY
  • Reo Yasuma
    Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY
  • Bradley D Gelfand
    Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY
  • Jayakrishna Ambati
    Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY
  • Footnotes
    Commercial Relationships Nagaraj Kerur, None; Younghee Kim, None; Yoshio Hirano, None; Valeria Tarallo, None; Ana Bastos-Carvalho, None; Benjamin Fowler, None; Tetsuhiro Yasuma, None; Reo Yasuma, None; Bradley Gelfand, None; Jayakrishna Ambati, iVeena (F), University of Kentucky (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2195. doi:
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      Nagaraj Kerur, Younghee Kim, Yoshio Hirano, Valeria Tarallo, Ana Bastos-Carvalho, Benjamin Fowler, Tetsuhiro Yasuma, Reo Yasuma, Bradley D Gelfand, Jayakrishna Ambati; Myd88 as a therapeutic target for choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2195.

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

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Abstract 
 
Purpose
 

Choroidal neovascularization (CNV), the hallmark of neovascular age-related macular degeneration (NV-AMD) is characterized by the invasion and leakage of choroidal blood vessels into neural retina. Recently we demonstrated that Myd88 dependent pathways mediate RPE degeneration in geographic atrophy, the other advanced form of AMD. Interestingly about 1/3rd of the GA patients are known to progress into NV-AMD. Therefore goal of the present study was to determine the role of Myd88 signaling pathways in the development of CNV.

 
Methods
 

CNV induction in mouse was performed following standard laser photocoagulation method. Choroidal angiogenesis volumes were measured by scanning laser confocal microscopy with 0.5% FITC-conjugated Isolectin B4. Activation of Myd88 signaling was assessed by examining the phosphorylation of IRAK4. Intraocular administration of neutralizing antibodies, cholesterol conjugated siRNAs and Myd88 inhibitory peptides was accomplished by intravitreous injection.

 
Results
 

The blockade of Myd88 signaling by genetic ablation, siRNA mediated knockdown or pharmacological intervention suppressed choroidal angiogenesis. Furthermore Myd88 activation in the mouse model of CNV was independent of TLR 2, 3, 4, 7 and 9. Inhibition of IRAK4, a signaling molecule downstream of Myd88, also suppressed laser induced CNV.

 
Conclusions
 

Our findings demonstrate that Myd88 mediated immune pathways play critical role in the mouse model of choroidal neovascularization. Therefore Myd88 offers a novel therapeutic target for neovascular AMD.

 
Keywords: 412 age-related macular degeneration  
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