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Yujuan Wang, Jiangna Chen, Zhijian Jiang; In vivo observation of keratocyte activation in a model of endothelial keratopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3907.
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© ARVO (1962-2015); The Authors (2016-present)
Keratocytes are neural crest-derived fibroblast cells in corneal stroma. Keratocytes are normally quiescent, but they can readily respond following injury. As the major neighbor cell to the corneal endothelium, we aim to evaluate keratocyte activation in vivo to illustrate the possible influence of endothelial cells and possible inflammatory pathogenesis in endothelial keratopathy.
We created a corneal endothelial dysfunction model in New Zealand White rabbits (1.5-2 kg) by scraping corneal endothelial cells about 9 mm in diameter. Slit-lamp examination, anterior segment optical coherence tomography measuring central corneal thickness (CCT), confocal microscopy, proinflammatory cytokine transcript expressions and histology evaluation were performed before endothelial scraping and at 1, 3, 7, 14, 30 and 60 days after the surgery.
All the corneas were opaque and moderately to severely edematous at day 1 (normal 385 (mean)±9.53 (SE) µm vs 1133±55.71 µm, p<0.0001) and at day 3 (normal 385±9.53 µm vs 741.9±136.7 µm, p=0.0002); but regained transparency and normal thickness since day 7 (normal 385±9.53 µm vs 370.5±19.92 µm, p=0.46). In the posterior portion of corneal stroma, confocal microscopy detected many highly reflective activated keratocytes in a multiple dendritic cell-like shape with multiple long extensions. These activated keratocytes returned to their original quiescent form at 30-60 days after surgery, showing small oval nuclei without processes. During the same period, the endothelial cells are fully regenerated, but had lower endothelial cell counts at 60 days (normal 2587±92.6 cells/mm2 vs 1733±106.61 cells/mm2, p<0.0001). Interleukin-1 beta (Il1β), tumor necrosis factor alpha (Tnfα), Il6 transcripts were upregulated in activated keratocytes vs quiescent ones (all p values<0.05). Historically, keratocytes with enlarged nuclei and long processes were noted microscopically at 1, 3, 7, 14 postoperative days, binucleated cells were also seen in the posterior stroma frequently; most keratocytes were quiescent at 30 and 60 days.
Our study showed keratocytes activation with proinflammatory cytokine upregulation in a rabbit model of endothelial keratopathy. Endothelial cell dysfunction might contribute to keratocyte activation, which in turn influences corneal homeostasis via inflammatory pathway in endothelial keratopathy.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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