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T. Ide, K. Nishida, M. Yamato, Y. Hori, N. Maeda, T. Okano, Y. Tano; Topical Application for Corneal Regression and Haze in an in vitro Model . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2727.
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PRK and LASIK have become popular methods for the correction of refractive errors. However, regression and haze remain serious post–operative complications. Aside form steroids, beta blockers were reported to prevent or reverse haze and regression in clinical studies, but there have been no experimental reports. We therefore examined the effects of beta blockers on keratocytes, and we performed basic research on regression and haze using an in vitro model.
For gel contraction assay, keratocytes were cultured in a collagen gel matrix to set keratocytes more in–vivo–like state. To observe cell morphology, cells were seeded into the gels or into the well of 12 well culture plates. To analyze myofibroblast markers, collagen type III (Col 3) and alpha smooth muscle actin (αSMA) mRNA expression indices were assessed by real–time quantitative RT–PCR. In each experimental system, a defined volume of various eye drops was added to the medium.
In addition to beta blockers, various IOP–reducing agents and other eye drops frequently used after refractive surgery were applied for screening and comparison in this study. Among the examined medications, carteolol hydrochloride (Mikelan®) and diclofenac sodium (Diclod®) inhibited gel contraction significantly, but timolol maleate (Timoptol®) did not. Keratocytes treated by Mikelan® became more polygonal on the well and more spherical within the gels, whereas keratocytes treated by other agents or controls showed fibroblastic appearance. Col 3 mRNA expression levels in cells treated with non–selective beta blockers (Timoptol® and Mikelan®) were significantly lower than the expression level when treated with other drugs. In contrast, αSMA expression level did not show a significant difference.
It is worth trying these beta blockers and Diclod® clinically, in particular Mikelan®, to prevent regression and corneal haze after refractive surgeries. If successful, these pharmacological effects can likely be applied not only to post–refractive surgeries, but also to situations in which activated fibroblasts play a role.
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