Systemic analysis of interferon-gamma inducible factor-10 (IP-10) as early biomarker for age-related macular degeneration

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Investigative Ophthalmology & Visual Science



Age-related macular degeneration (AMD) is a chronic diseasethat develops over decades and may lead to severely damagedvision. Currently the diagnosis of AMD is based on visual diagnosis.It is generally accepted that the pathological process thatleads to AMD begins much earlier in life. Very early diagnosisof AMD and identification of subjects that are at high riskfor future development of AMD will become critical as new therapeuticagents are studied to battle dry AMD. We have previously identifiedinterferon-inducible factor-10 (IP-10) as one of the pro-inflammatorychemokines in the sera subjects with AMD. In this study we haveinvestigated the potential cellular sources of IP-10 in subjectswith AMD, especially whether there are any significant systemiccontributions.


Subjects with AMD were clinically classified as one of the followingphenotypes, AREDS stages 1 and 3, geographic atrophy and neovascularAMD. Sera were collected and subjected to Bio-plex assay forIP-10 and related pro-inflammatory factors. Buffy coats werederived from whole blood samples and subjected to flow cytometryanalysis for expression of IP-10 and its cognate receptor, CXCR3in the circulating leukocyte fraction. Postmortem eye and spleensamples were collected. Eyes were staged for the stage of AMDor control and correlated with expression of IP-10 and CXCR3in both eyes and matched spleens using immunohistochemistry(IHC).


Serum IP-10 levels were significantly elevated in all stagesof AMD (P<0.07). The peak of serum IP-10 concentration wasat AREDS stage 3. Flow cytometry showed that circulating leukocytesexpressed this chemokine system and probably contribute to elevatedserum IP-10 levels. IHC of matched spleens of AMD donors showedthat IP-10 expression was elevated in spleen leukocytes as earlyas early stage AMD. Similarly, in postmortem eyes with earlyAMD, IP-10 expression was increased in the RPE and subsequentlyin basal linear/laminar deposits in all other stages of AMD.


Our results indicate that IP-10 may be a good candidate biomarkerfor early diagnosis of AMD and that systemic sources such ascirculating and splenic leukocytes participate in maintenanceand elevation of IP-10 levels.