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Stephanie M Ecker, Travis M Poulsen, Joshua C Hines, Bert M Glaser; Changes in the Vitreous Proteome One Month Following Initial Anti-VEGF Treatment for Wet AMD Correlate with Treatment Response. Invest. Ophthalmol. Vis. Sci. 2014;55(13):570.
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© ARVO (1962-2015); The Authors (2016-present)
To explore the changes of protein expression levels in the vitreous of wet AMD patients before and after the initial anti-VEGF treatment comparing patients who gain visual acuity to patients who have stable or worse visual acuity.
There were 132 wet AMD eyes included in this study. All of these eyes were treatment naïve. The best Corrected ETDRS visual acuity was measured, and vitreous of each eye was sampled, just prior the initial and one month following anti-VEGF injection. Each vitreous sample was assessed via Reverse Phase Protein Microarray technology to measure the levels of 45 proteins from biochemical processes known to be important in the progression of wet AMD, these pathways included, Angiogenesis, Inflammation, Apoptosis/Survival, Oxidative Stress, and Hypoxia. Changes in the levels of these proteins were compare between those who gained any vision (n=63) and those who lost vision (n=69). These proteins were also compare between: those who gained ≥5 ETDRS letters (n=46) versus those who lost ≥ 5 letters (n=46); and those who gained ≥ 10 letters (n= 25) versus those who lost ≥ 10 letters (n=37).
When comparing the vitreous proteome before and after anti-VEGF treatment three proteins were significantly higher after treatment. The increase was observed whether the patients gained any letters, ≥ 5 letters or ≥ 10 letters (P- values listed respectively): VEGFR2 Tyr996 (P= 0.0019, P= 0.0015, and P= 0.017), MMP-14 (P= 0.0032, P= 0.0036, and P= 0.0351), and BAD Ser112 (P= 0.0032, P= 0.005, and P= 0.045). On the other hand, when eyes that lost letters only MMP2 showed significant change. MMP2 was significantly higher after treatment in the vitreous of eyes that lost any letters (P= 0.032), and in eyes that lost ≥ 5 letters (P= 0.042). However, protein levels of eyes that lost ≥10 letters showed no significant changes among any protein in the panel. Interestingly, VEGFA levels showed no change from before to after anti-VEGF treatment in any of the groups.
Changes in levels of specific protein following the initial anti-VEGF treatment correlating with visual response may give further insight into the role proliferative pathways, tissue invasion pathways and cell survival pathways that may guide the search for new therapeutic agents.
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