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Keratoconus: a reversible condition?

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First Author: A.Song UK

Co Author(s):    A. Song   R. Gouveia   C. Connon              

Abstract Details

Purpose:

Keratoconus, a corneal ectasia leading to a progressive thinning and deformation of the corneal stroma, causes irregular astigmatism and a decrease in visual acuity. Despite a worldwide prevalence of 1:2000, the aetiology of this condition is unknown. The development of a human in vitro model is necessary to study the disease process and therefore discover novel treatment modalities.

Setting:

To create an in vitro model of the keratoconic corneal stroma to explore the impact of surface geometry and of all-trans retinoic acid (RA)-supplemented low-glucose medium conditions in alleviating phenotypic variations between keratoconic and healthy corneal stromal cells (keratocytes).

Methods:

Keratocytes (1×105 cells) were seeded in the periphery of curved vials and cultured in serum medium, high-glucose (4.5 g/L) serum-free medium, and low-glucose (2 g/L) serum-free medium supplemented with RA (LG+RA) for 2 months to allow tissue formation. Cell proliferation, alignment, and gene expression were assessed at the end of the culture period.

Results:

LG+RA successfully reversed some of the phenotypic hallmarks of keratoconic keratocytes, with cells within curved model tissues showing significantly higher cell proliferation (p=0.0008), cell alignment (p<0.0001), and transcription of stroma-characteristic markers such as KERA (p=0.0002) and ALDH3A1 (p=0.0489). Moreover, LG+RA medium inhibited the expression of MMP1, a matrix metalloproteinase up-regulated in keratoconus.

Conclusions:

Surface curvature and medium composition were found to have a synergistic effect in reversing important phenotypic aspects of keratoconic keratocytes. This has important clinical indications for the use of RA to treat or halt the progression of keratoconus.

Financial Disclosure:

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