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Marina Hovakimyan, Rudolf F Guthoff, Klaus P Schmitz, Oliver Stachs; Modulating Wound Healing after Collagen Cross-linking. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4701.
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Corneal Cross-Linking (CXL) is an established minimally-invasive procedure for the treatment of corneal thinning in keratoconus and post-LASIK-ectasia. However, a complete keratocyte loss after CXL and an associated risk for corneal opacification and melting still remains an unwanted treatment effect. In the present study we examine, whether a regenerating matrix therapy agent (RGTA, Cacicol®) which has already been shown to be effective in the treatment of chronic corneal ulcers, could positively influence the cell regeneration.
New Zealand White albino rabbits were divided in three groups, in which the corneae underwent CXL according to the standard protocol. While in the control group (1) no further medication was performed, the two additional groups were instilled with two drops of CACICOL20 before (2) or after (3) CXL. Epithelial healing was examined by fluorescein-staining and keratocyte regeneration was evaluated using in vivo confocal laser-scanning microscopy (Heidelberg Retina Tomograph/Rostock Cornea Module) for up to one week. The epithelial morphology and keratocytes distribution was examined histologically using DAPI and Hemalaun/Eosin staining.
Three days after CXL all corneae were significantly swollen and demonstrated a complete cell loss throughout the entire thickness. Morphologically, no differences were seen between CACICOL-treated (2, 3) and untreated (1) groups at that time point. One week post-treatment, the anterior and middle stroma was completely devoid of cells in the control group (1) and only typical dendritic like optical elements, corresponding to the cell remnants were visualized. In contrast, the CACICOL-treated animals (2, 3) revealed hyperreflective repair keratocytes in the middle and also in the anterior stroma. Migrating spindle-shaped activated keratocytes were observed in the posterior stroma.
In our previous studies we have demonstrated that the keratocyte density remains significantly reduced for up to 20 weeks after CXL. Here, we have the first evidence that the keratocyte repopulation can be accelerated by applying a new ophthalmologic solution based RGTA technology. It should be mentioned, however, that these results are preliminary, and need to be quantitatively confirmed further in a larger group of animals.
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