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J. Head, D. Shen, M. Zhou, R. A. Garfinkel, C.-C. Chan; Expression of Clusterin and VEGF in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4976. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) is an ocular complication of diabetes mellitus that is responsible for many cases of new blindness each year in the US. The hallmark of DR is retinal microvascular damage, which leads to ischemia, neovascularization, hemorrhage and blindness. The mechanisms behind DR are unclear, but many factors may contribute to this complex process. Our goal was to elucidate the role of certain biomarkers associated with DR. While VEGF is elevated in the sera and eyes of patients with DR, little is known about other biomarkers including clusterin, a glycoprotein and chaperone involved in the response to ischemia.
We examined 12 vitreous specimens and an eye from DR patients. Vitreous samples were cytospinned, after which clusterin, CXCL12, and VEGF levels were measured by ELISA of the supernatant. The precipitates were processed for cytology and immunohistochemistry (IHC) using antibodies against VEGF, clusterin, and CXCR4. Microdissection was used to harvest cells and molecular analysis (RT-PCR) was used to determine mRNA expression in each isolate. The eye was also examined using IHC and RT-PCR.
ELISA showed increased intravitreal levels of VEGF and clusterin proportional to the severity of disease. IHC showed strong immunoreactivity against clusterin and weak reactivity against CXCR4 in fibrovascular fragments. RT-PCR was successful in 7 of 12 samples; 7/7 showed higher expression of VEGF and 3/7 of clusterin mRNA when compared to a normal control (see Table for fold increase in expression; ND = not detected). There is no correlation between clusterin and VEGF expression. The DR eye demonstrated increased clusterin deposition in retinal vascular lesions.
Our findings suggest that clusterin, independent of VEGF, may be a useful index of DR and play important role in the pathogenesis of this disease. Further study is needed to better understand the role of clusterin in both proliferative and non-proliferative DR.
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