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Fang Xie, Dawei Sun, souska Zandi, Shintaro Nakao, Ali Hafezi-Moghadam; Molecular Imaging of Retinal Endothelial Changes in Experimental Glaucoma: A Novel Approach to Early Diagnosis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3525.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is a common disease that leads to progressive visual loss. Increased intraocular pressure (IOP) is a major risk factor, however, the pathogenesis of the disease remains unclear. There is a great need for early diagnostic tools of retinal changes, as vision loss is preventable with early detection and treatment. High IOP causes release of tumor necrosis factor-α (TNF-α) in the retina, which ultimately leads to retinal ganglion cell (RGC) loss. TNF-α causes inflammatory changes in retinal, such as adhesion molecule upregualtion. We introduce a novel molecular imaging approach that detects early retinal endothelial expression secondary to elevated IOP.
Molecular imaging probes were custom-designed by covalently conjugating carboxylated fluorescent microspheres (MSs, 2µm) with recombinant PSGL-1 and anti-ICAM-1-mAb. MSs were injected into the tail vein of normal and IOP animals. MS interaction in the fundus vessels was studied using a scanning laser ophthalmoscope. 30min after MS injection, rats were perfused with PBS and rhodamine-labeled conA. Flatmounts were prepared for ex vivo evaluation of accumulated MS and leukocytes. Increased IOP in rats was caused by the established technique of saline injection into anterior chamber through the corneoscleral limbus. The saline bottle was placed at a height of 70cm above the animal eye for 60min. Ocular pressure was regularly measured by a Tono-Pen.
Acutely elevated IOP caused a significant increase in leukocyte accumulation (207.3±46.5, P<0.05) in retinal vessels. In animals with high IOP molecular imaging probes bound significantly more in retinal vessels compared to normal controls (P<0.05). TNF-α was significantly elevated 12h after acute IOP elevation, while it was at undetectable levels in normal animals at the time of experimental glaucoma induction. Histological ex vivo examinations of the retinal and choroidal tissues confirmed significantly higher binding of the molecular imaging probes and firm adhesion in animals with IOP.
The present work introduces a novel non-invasive approach to detection of molecular and cellular consequences of elevated IOP. The pattern and dynamic of expression of retinal endothelial injury markers provides valuable information about disease progression. Our molecular imaging approach could be further developed to detect subclinical signs of retinal damage in glaucoma patients.
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