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Stephanie Ecker, Joshua Hines, Ann Igbre, Bert Glaser; The Composition of the Vitreous Proteome in Patients with Wet AMD Can Differentiate Between CNV and RAP: An Important New Diagnostic Tool. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4116. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Neovascular age related macular degeneration (AMD) is a complicated, heterogeneous disease. Among the various phenotypes of wet AMD, two significant disease subsets are those who develop from retinal angiomatous proliferation (RAP) and those who develop from choroidal neovascularization (CNV). Recent studies have shown that the Vitreous Proteome can reflect disease activity and response to treatment in wet AMD. We therefore sought to determine if there are characteristics of the Vitreous Proteome that differentiate RAP from primary CNV.
Multiple in-office vitreous aspirations of 50-100µL were obtained from 106 patients who presented with neovascularization initiating from RAP (n=56) or CNV (n=50). The aspirations analyzed were taken prior to the patient receiving intra-vitreal bevacizumab but no laser. All vitreous aspirations (128 RAP, 109 FV CNV) were evaluated for 45 proteins using Reverse Phase Protein Microarray Technology (RPPM). The proteins evaluated were chosen because they represent biochemical pathways involved in inflammation, apoptosis, hypoxia/oxidative stress and proliferation/angiogenesis.
: Seven of the 45 proteins demonstrated significant differences between the two AMD phenotypes of RAP and CNV. Complement Components C5a and C9, along with Complement Factor H are expressed at higher levels in patients with RAP (p= 0.0101, p= 0.0497, p= 0.0442). Additionally, Matrix Metalloproteinase 9, 14 (MMP-9, MMP-14) and Tissue Inhibitor of Metalloproteinase-2 (TIMP2) are expressed at higher levels in RAP patients (p= 0.0125, p= 0.0002, and p= 0.0022). Lastly, COX2 is expressed at higher levels in the vitreous of patients with RAP, p= 0.0035.
This is the first time that the Vitreous Proteome of AMD patients with neovascularization initiating from RAP versus those with primary CNV has been compared to determine protein expression differences. The differing levels of proteins involving the complement system and matrix metalloproteinases suggests that these protein families could serve as potential biomarkers to predict development of these types of vessel pathologies and at the same time shows that there is a difference in the pathobiology of differing phenotypes of wet AMD. These finding may suggest different approaches to the management of AMD depending upon the status of the Vitreous Proteome.
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