Unfolded protein response in fuchs endothelial corneal dystrophy: a unifying pathogenic pathway?

American Journal of Ophthalmology
Christoph EnglerAlbert S Jun

Abstract

To assess for activation of the unfolded protein response in corneal endothelium of Fuchs endothelial corneal dystrophy patients. Retrospective, comparative case series of laboratory specimens. Corneal specimens of patients with Fuchs dystrophy and controls with corneal pathologic features other than Fuchs dystrophy were evaluated by transmission electron microscopy (TEM) to evaluate for structural changes of the rough endoplasmic reticulum in corneal endothelium. TEM images were evaluated for alterations of rough endoplasmic reticulum as a sign of unfolded protein response. Normal autopsy eyes, Fuchs dystrophy corneas, and keratoconus corneas were used for immunohistochemistry. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections of patient corneas for 3 unfolded protein response markers (GRP78, the alpha subunit of eukaryotic initiation factor 2, C/EBP homologous protein) and 2 apoptosis markers (caspase 3 and 9). Immunohistochemistry signal quantitation of corneal endothelium for evaluation of marker expression was performed using automated software. Corneal sections were assessed quantitatively for levels of immunohistochemistry marker expression. TEM showed enlargement of rough endoplasmic retic...Continue Reading

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