Abstract
Purpose: :
This study aimed to profile the soluble, activated VEGF receptors in the vitreous of eyes with wAMD during the course of bevacizumab treatment, versus non-proliferative control samples.
Methods: :
164 in-office vitreous samples were obtained from 41 wAMD patients. Vitreous was aspirated from 24 control eyes prior to undergoing vitrectomy for macular hole or retinal detachment. Each wAMD patient was treatment naïve with the sample taken before initiation of anti-VEGF treatment, and also before each of the next three subsequent treatments. All samples were aspirated via pars plana approach, utilizing a 25 gauge needle with 1 mL syringe directed mid-vitreous cavity and collecting approximately 0.05 to 0.10 mL. Samples were then probed for VEGF-A along with VEGFR2 Tyr951, Tyr996, & Tyr1175, by way of Reverse Protein Microarray (RPPA). Patients who’s VA measurement increased by ≥10 letters (ETDRS) were considered responders, while everyone else was a non-responder.
Results: :
A total of 41 patients were included; 14 were responders while 27 were non-responders. There was a statistically significant difference (P=0.0082) in VEGFR2 Tyr951 between responders (mean [SEM], 2.183 [.1769] relative value units (RVU)) and non-responders (mean [SEM]. 1.622 [.1082] RVU). There is also a significant difference (P=0.0259) between responders and controls (mean [SEM] 1.635 [.1625] RVU) also in VEGFR2 Tyr951. However, there is no significant difference between the non-responder and control treatment response groups.
Conclusions: :
A significant amount of research now points to VEGFR2 as a major signal transducer in angiogenic disease states. Mapping activated VEGF receptors therefore becomes crucial to fully understanding initiation of angiogenesis. Vitreous VEGF-A showed no significant difference between responders and non-responders, however the activated receptor VEGFR2 Tyr951 showed a significant difference between responders and non-responders as well as controls. Past studies have implicated VEGFR2 Tyr951 as a critical regulator of endothelial cell migration, as well as active angiogenesis. To fully understand the role of angiogenesis in wAMD, VEGFR2’s role in phosphorylation must be understood biochemically.
Keywords: growth factors/growth factor receptors • age-related macular degeneration • clinical laboratory testing