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Desiree Cyr, Seyda F. Absar, Fong Ming Mo, Alan Proia, Kameran Lashkari; Systemic Analysis Of Interferon-inducible Factor-10 (ip-10) As Early Biomarker For Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2338.
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Age-related macular degeneration (AMD) is a chronic disease that develops over decades and may lead to severely damaged vision. Currently the diagnosis of AMD is based on visual diagnosis. It is generally accepted that the pathological process that leads to AMD begins much earlier in life. Very early diagnosis of AMD and identification of subjects that are at high risk for future development of AMD will become critical as new therapeutic agents are studied to battle dry AMD. We have previously identified interferon-inducible factor-10 (IP-10) as one of the pro-inflammatory chemokines in the sera subjects with AMD. In this study we have investigated the potential cellular sources of IP-10 in subjects with AMD, especially whether there are any significant systemic contributions.
Subjects with AMD were clinically classified as one of the following phenotypes, AREDS stages 1 and 3, geographic atrophy and neovascular AMD. Sera were collected and subjected to Bio-plex assay for IP-10 and related pro-inflammatory factors. Buffy coats were derived from whole blood samples and subjected to flow cytometry analysis for expression of IP-10 and its cognate receptor, CXCR3 in the circulating leukocyte fraction. Postmortem eye and spleen samples were collected. Eyes were staged for the stage of AMD or control and correlated with expression of IP-10 and CXCR3 in both eyes and matched spleens using immunohistochemistry (IHC).
Serum IP-10 levels were significantly elevated in all stages of AMD (P<0.07). The peak of serum IP-10 concentration was at AREDS stage 3. Flow cytometry showed that circulating leukocytes expressed this chemokine system and probably contribute to elevated serum IP-10 levels. IHC of matched spleens of AMD donors showed that IP-10 expression was elevated in spleen leukocytes as early as early stage AMD. Similarly, in postmortem eyes with early AMD, IP-10 expression was increased in the RPE and subsequently in basal linear/laminar deposits in all other stages of AMD.
Our results indicate that IP-10 may be a good candidate biomarker for early diagnosis of AMD and that systemic sources such as circulating and splenic leukocytes participate in maintenance and elevation of IP-10 levels.
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