To evaluate levels of 37 native pathway proteins of the vitreous proteome from a subset of wet age-related macular degeneration (AMD) patients with and without subretinal fluid (SRF).


A total of 62 consecutive samples were aspirated from 12 patients with AMD, six who had SRF at baseline, and six who did not have SRF at any point during the study. Vitreous levels of the 37 native pathway proteins were analyzed in these patients using reverse phase protein microarray technology. At each visit, at which the 62 samples were taken, SRF and central retinal thickness were measured. These values were then compared to the relative intensity level of the 37 proteins screened.


In the subset of AMD patients with SRF, the average matrix metalloproteinase 9 (MMP-9), interleukin (IL)-12, Abelson murine leukemia viral oncogene homolog 1 (cABL) Thr735, heme oxygenase-1, Musashi, platelet-derived growth factor receptor beta Tyr751 (PDGFRβ), IL-8, and BCL-2 associated death promoter (BAD) Ser112 levels in the vitreous were found to be significantly different with a 21%-82% increase in expression compared to those without SRF (p<0.0001). Within the SRF group, there was a positive correlation between the vitreous MMP-9 levels and the SRF level. MMP-9 levels in the vitreous proteome varied with the level of SRF but not retinal edema. Compared to patients without SRF, the patients with initial SRF had persistent or progressive disease.


This is the first prospective case series sequentially monitoring the vitreous proteome in patients with wet AMD. The results suggest that MMP-9 is a proteomic biomarker of SRF accumulation, separate from macular edema.