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B. Seitz, P. Charalambous, U. Löw, N. Kozeis, F. Schirra, W. Henn, Z. Gatzioufas; Evidence of Oxidative Stress in Schnyder Corneal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1002. doi: https://doi.org/.
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Schnyder corneal dystrophy (SCD) is a rare autosomal dominantly inherited corneal disorder affecting the central and peripheral corneal stroma and characterized by cholesterol deposition in the stroma due to abnormal lipid metabolism. The aim of our study was to examine the possible contribution of the nitric oxide (NO) pathway and lipid peroxidation to the pathogenesis of the disease.
Four eyes from three patients with SCD, who underwent penetrating keratoplasty (PK), were examined. Half of the SCD cornea was saved for electron microscopy (EM) and the other half was subjected to immunohistochemistry with antibodies against nitric oxide synthase (i-NOS and e-NOS) and nitrotyrosine (NT). During PK 15 µl of aqueous humor were aspired from the anterior chamber and high-performance liquid chromatography (HPLC) for detection of malondialdehyde (MDA) was conducted. MDA is the end-product of free-radical-initiated lipid peroxydation indicating oxygen-dependent degradation of polyunsaturated fatty acids. NOS isomers are responsible for the production of NO, the overproduction of which causes a cascade of oxidative damage. NT is considered to be a specific marker for nitrogen-related oxidants and, therefore, its presence provides evidence of oxidative damage.
Normal corneas demonstrated immunoreactivity for e-NOS in the epithelium, predominantly in the anterior layers. Immunostaining for i-NOS was minimal. In SCD corneas a strong signal for i-NOS was observed in the epithelium. Immunoreactivity for e-NOS was detected in a pattern similar to normal corneas. Immunolabeling for NT was strong in SCD corneas throughout the epithelium. Normal corneas displayed a minimal signal for NT. EM revealed numerous stromal electron-lucent spots representing areas of lipid deposition inside corneal keratocytes located in the superficial stroma as well as in the basic epithelial layer. HPLC revealed significant increased MDA levels in the aqueous humor of the SCD compared to the control patients (Fischer exact test, p<0.05).
Our results indicate that both increased production of NO as well as lipid peroxydation occur in patients with SCD, inducing a high level of oxidative stress. In view of these findings we assume that oxidative damage might play a key role in the pathophysiology of SCD.
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