Activated VEGF receptor shed into the vitreous in eyes with wet AMD: a new class of biomarkers in the vitreous with potential for predicting the treatment timing and monitoring response.
OBJECTIVE
To examine whether phosphorylated vascular endothelial growth factor (VEGF) receptors shed into the vitreous reflect the ongoing retinal and choroidal signal pathway activity in wet age-related macular degeneration (AMD).


METHODS
Vitreous samples obtained immediately prior to anti-VEGF injection from 11 patients with choroidal neovascularization were analyzed using reverse-phase microarrays. Two patients had samples collected at the time of injection and 1 month later. Samples from 5 patients were collected prior to vitrectomy for macular hole, epiretinal membrane, or retinal detachment.


RESULTS
Phosphorylated forms of VEGF receptor (VEGFR Y996 and Y1175), platelet-derived growth factor receptor beta (PDGFRbeta Y716 and Y751), and c-KIT (Y703) were present in the vitreous. A significant difference in PDGFRbeta Y751 (P < .002), VEGFR Y996 (P < .04), and VEGFR Y1175 (P < .006), but not c-KIT Y703 (P < .05) or PDGFRbeta Y716 (P < .96), was noted for the responders to treatment (n = 5) compared with nonresponders (n = 6) and controls (n = 5).


CONCLUSIONS
Vitreous levels of activated receptors constitute a new class of biomarkers. Activated forms of VEGF and PDGF receptors, previously not known to exist in the vitreous, correlate with response to anti-VEGF therapy. These findings could provide the basis for the development of individualized treatment and discovery of new therapeutic targets.
The National Retina Institute, Towson, MD 21204, USA.
Geetanjali
G
Davuluri
Virginia
V
Espina
Emanuel F
EF
Petricoin
Mark
M
Ross
Jianghong
J
Deng
Lance A
LA
Liotta
Bert M
BM
Glaser
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015415:Biomarkers / Q000378:metabolism*; D020256:Choroidal Neovascularization / Q000188:drug therapy / Q000378:metabolism*; D019773:Epiretinal Membrane / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D005260:Female; D006801:Humans; D007267:Injections; D008268:Macular Degeneration / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D040081:Protein Array Analysis; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D012163:Retinal Detachment / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D012167:Retinal Perforations / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D019009:Proto-Oncogene Proteins c-kit; D020797:Receptor, Platelet-Derived Growth Factor beta; D040262:Receptors, Vascular Endothelial Growth Factor