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Hironori Uehara, Christina Mamalis, Ruth E Hogg, Usha Chakravarthy, Balamurali Ambati; Soluble isoform of Flt1 differentiates those with neovascular AMD from those with early AMD. Invest. Ophthalmol. Vis. Sci. 2014;55(13):666. doi: https://doi.org/.
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Age-related macular degeneration (AMD) is a leading cause of blindness. Recently, we showed the decoy VEGF receptor, soluble Flt-1 (sFlt-1) in RPE is mechanistically required for subretinal vascular demarcation. Moreover, patients with neovascular AMD (nAMD) expressed less sFlt1 in the RPE. sFlt-1 is also found in serum and other tissues. We hypothesized that serum sFlt-1 might be reduced in patients with nAMD. This study explored the relationship between serum Flt-1 and AMD severity.
Serum levels of sFlt-1 were assessed in patients with nAMD in at least one eye (n=97), early AMD (n=53) and age-matched controls (n=56) using Human sVEGF R1/Flt-1 Quantikine ELISA Kit (R&D, USA). A logistic regression model was used to determine the effects of sFLT level on the stage of macular degeneration (AMD stage) as defined by the AREDS staging system, models were adjusted for age, gender and smoking history.
sFlt-1 concentration of healthy, early AMD, and nAMD were 90.8±2.9 pg/mL (±SEM,), 88.2±2.6 pg/mL and 79.9±2.2 pg/mL respectively. sFLT from nAMD patient serum was significantly decreased (ANOVA, p<0.01). Controlling for gender and age, for each 10 point increase in sFLT the odds for having nAMD decreased by 27.0%; OR=0.730 (95% CI: 0.594-0.898, p=0.003).Controlling for gender and sFLT level, for each increase in year of age the odds for having nAMD increased by 12.8%; OR= 1.128(95% CI: 1.066-1.193, p <0.001).
Serum sFlt-1 is decreased in those with nAMD compared to controls and early AMD patients, this together with our previous report which showed that sFlt-1 was decreased in RPE of AMD patients, suggests sFlt-1 in serum is likely associated with development of wet AMD. Prospective studies are required to determine if serum sFlt-1 could be used as a prognostic biomarker of AMD progression.
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