Metabolic defect, oxidative stress may spur keratoconus

Invest Ophthalmol Vis Sci. 2008;49:4361-4369.

Cultured fibroblasts showed an innate, hypersensitive response to oxidative stressors in patients with keratoconus. Such hypersensitivity may contribute to the development and progression of keratoconus.

Marilyn Chwa, MS, and colleagues studied 11 normal corneas and 11 keratoconic corneas. Cultured corneal fibroblasts were exposed to neutral or low pH conditions with or without hydrogen peroxide. Low pH placed high metabolic stress on mitochondrial function. Hydrogen peroxide induced oxidative stress.

Keratoconic fibroblasts treated with low pH had significantly elevated levels of caspase-9 and caspase-12, cysteine proteases that are associated with metabolic stress, compared with normal corneas.

"Our findings suggest that in vivo intact [keratoconic] corneas may have both a metabolic defect and high levels of oxidants that contribute to damaged mtDNA found in the intact [keratoconic] corneas," the study authors said in the October issue of Investigative Ophthalmology & Visual Science.

This study helps to elucidate further the basic mechanisms for potential progression of keratoconus, which in general has been poorly understood from the aspect of the exact mechanism of disease causation. At the present time, this study doesn’t affect our current clinical practice, but if the mechanisms of the relationship between oxidative stress and disease progression are further understood, this may lead to new therapeutic options for patients with keratoconus.

Further research in this field may help to elucidate the basic science mechanisms that lead to the corneal instability and vision loss from keratoconus. This would be welcome news for patients with keratoconus and their eye care providers.

– David R. Hardten, MD
OSN Cornea/External Disease Section Member