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Ana Cristina Riestra, Almudena Íñigo-Portugués, Enol Artime, Paola Braga, Jesus Merayo-Lloves, Ignacio Alcalde; Effectiveness of regenerative drops (CALCICOL) on corneal ulcers (post-PRK) in an experimental animal model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5176.
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© ARVO (1962-2015); The Authors (2016-present)
This study poupose is to evaluate the effectiveness of application of CACICOL, regenerative therapy based on heparan sulfate derivatives, in an experimental mice model of corneal ulcer after photorefractive keratectomy (PRK).
Mice were subjected to PRK surgery with a 2.0 mm ablation zone on the central cornea and 45 mm of depth on a VISX Star S2 excimer laser. Corneas were treated topically with one drop of CACICOL 1 hour and 48 hours after injury. Control groups received BSS (Balanced Salt Solution) in the same posology. Clinical and histopathological events were evaluated at 1, 2, 3 and 7 days after surgery. For histological analysis, sections were obtained through the central region of the corneas and used to analyze the general aspect of injured and healed corneas using Hematoxylin and eosin staining. Adjacent sections were used to immunofluorescence analysis using antibodies to Ki67 (proliferation), αSMA (myofibroblast transformation), E Cadherin (assembly of epithelial cells) and neuronal class III β-tubulin (innervation). TUNEL assay was performed to estimate the number of apoptotic cells.
Corneas treated with CACICOL showed a greater degree of transparency compared to BSS treated mice and a higher speed of closure of the wounded area during the first 24 hours. Corneas treated with CACICOL presented a thickness and an epithelial cytoarchitecture, based on E-cadherin labeling, similar to uninjured corneas, indicating a better organized regenerating process. 24 hours after treatment with CACICOL, a marked reduction (-50%) of the apoptotic cell density was observed but CACICOL seemed not to affect the proliferation rate during the wound healing process. Analysis of αSMA profiles in the stroma showed that CACICOL reduced or delayed the presence of myofibroblasts (-58%) in the stroma compared to BSS (p<0.001). Finally we described a putative neuroregenerative effect of CACICOL in corneas submitted to a PRK experimental lesion. Animals treated for 7 days with CACICOL showed an increased epithelial nerve terminal density of 62%.
In a model of laser induced cornea surgical lesions, Heparan sulfate derivatives (CACICOL) topical application could be involved in facilitating the correct assembly of epithelial cells, improving nerve regeneration, avoiding myofibroblast scarring formation or promoting the deposition of newly generated extracellular matrix.
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