RT Journal Article
A1 Kerur, Nagaraj
A1 Kim, Younghee
A1 Hirano, Yoshio
A1 Tarallo, Valeria
A1 Bastos-Carvalho, Ana
A1 Fowler, Benjamin
A1 Yasuma, Tetsuhiro
A1 Yasuma, Reo
A1 Gelfand, Bradley D
A1 Ambati, Jayakrishna
T1 Myd88 as a therapeutic target for choroidal neovascularization
JF Investigative Ophthalmology & Visual Science
JO Invest. Ophthalmol. Vis. Sci.
YR 2014
VO 55
IS 13
SP 2195
OP 2195
SN 1552-5783
AB  PurposeChoroidal 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. MethodsCNV 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. ResultsThe 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. ConclusionsOur 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. 
RD 4/11/2021