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Jayant V. Iyer, John Connolly, Bijin Au, Tun Kuan Yeo, Rupesh Agrawal, Stephen C. Teoh; Proteomic Analysis of Aqueous Humor in Patients with Cytomegalovirus Retinitis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2786.
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© ARVO (1962-2015); The Authors (2016-present)
To analyze the comprehensive ocular proteomic cytokine, chemokines and growth factor composition of patients with cytomegalovirus retinitis (CMVR).
Seventeen samples were obtained by aqueous paracentesis from 14 patients diagnosed with clinical CMVR receiving intravitreal ganciclovir therapy. There were 15 samples from patients with HIV, and 2 samples from patients with autoimmune disease on immunosuppression. Eleven control samples were obtained from 11 patients with no other ocular disease undergoing routine cataract surgery. Aqueous humor fractions were analyzed for the concentration of 42 different cytokines, chemokines and growth factors thought to be involved in viral induced inflammation, with the Luminex® (Bio-Plex 200) platform. The specific inflammatory signature of protein expression in CMVR patients relative to controls was assessed by multivariate analysis using the GeneSpring® software package.
Of the 42 factors analyzed, 36 were expressed at some level in patient samples. A common signature of infection was revealed in patients with CMVR dominated by the expression of the chemokines fractalkine, IP-10 and MCP-1, the cytokine IL1-alpha and the growth factors EGF and FLT3-ligand when compared with the control group. Statistically significant differences were observed between cases and controls for all analytes in the signature; IL1-alpha (p=0.001), MCP-1 (p=0.002), EGF (p=0.003), fractalkine (p=0.009), IP-10 (p=0.019), FLT3-ligand (p=0.021). Interestingly the intraocular levels of fractatikine, a highly bioactive leukocyte chemotactic agent, demonstrated an inverse correlative trend with the levels of circulating CD4+ T-cell in patients.
Proteomic profiling of aqueous humor in patients with CMVR has revealed a pronounced and consistent proteomic immune signature which was apparent even in the relatively small patient sample size. The signature shares features of localized viral induced inflammation and is characteristic of a tissue specific myeloid/granulocytic response. This observation is supported by the absence of detectable intraocular T-cell derived cytokines during infection. The association with intraocular fractalkine levels and adaptive immune dysfunction, as measured by circulating CD4 T-cell counts, may reflect a specific suppression in anti-CMV immunity. A more extensive cohort analysis may be required to test this hypothesis. Further longitudinal analysis may help elucidate the underlying processes involved in CMV eye disease. This may lead to development of novel, targeted treatment strategies for CMVR in the near future.
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