PURPOSE: To assess for activation of the unfolded protein response in corneal endothelium of Fuchs endothelial corneal dystrophy patients. DESIGN: Retrospective, comparative case series of laboratory specimens. METHODS: 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. RESULTS: TEM showed enlargement of rough endoplasmic reticulum in corneal endothelium of all Fuchs dystrophy specimens. Immunohistochemistry quantitation demonstrated a significant increase in mean signal in corneal endothelium from Fuchs dystrophy patients for markers GRP78, the alpha subunit of eukaryotic initiation factor 2, C/EBP homologous protein, and caspase 9 compared with non-Fuchs dystrophy corneas (P < .05). CONCLUSIONS: Results of both TEM and immunohistochemistry indicate activation of unfolded protein response in Fuchs dystrophy. Unfolded protein response activation leads to endothelial cell apoptosis in Fuchs dystrophy and may play a central pathogenic role in this disease. Copyright (c) 2010 Elsevier Inc. All rights reserved.
PURPOSE: To assess for activation of the unfolded protein response in corneal endothelium of Fuchs endothelial corneal dystrophypatients. DESIGN: Retrospective, comparative case series of laboratory specimens. METHODS: 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. RESULTS: TEM showed enlargement of rough endoplasmic reticulum in corneal endothelium of all Fuchs dystrophy specimens. Immunohistochemistry quantitation demonstrated a significant increase in mean signal in corneal endothelium from Fuchs dystrophypatients for markers GRP78, the alpha subunit of eukaryotic initiation factor 2, C/EBP homologous protein, and caspase 9 compared with non-Fuchs dystrophy corneas (P < .05). CONCLUSIONS: Results of both TEM and immunohistochemistry indicate activation of unfolded protein response in Fuchs dystrophy. Unfolded protein response activation leads to endothelial cell apoptosis in Fuchs dystrophy and may play a central pathogenic role in this disease. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Authors: Tetsuya Toyono; Tomohiko Usui; Guadalupe Villarreal; Laura Kallay; Mario Matthaei; Lucas M M Vianna; Angela Y Zhu; Masahiko Kuroda; Shiro Amano; Albert S Jun Journal: Cornea Date: 2016-11 Impact factor: 2.651
Authors: Huan Meng; Mario Matthaei; Narendrakumar Ramanan; Rhonda Grebe; Shukti Chakravarti; Caroline L Speck; Martha Kimos; Neeraj Vij; Charles G Eberhart; Albert S Jun Journal: Invest Ophthalmol Vis Sci Date: 2013-03-28 Impact factor: 4.799
Authors: Mario Matthaei; Jianfei Hu; Huan Meng; Eva-Maria Lackner; Charles G Eberhart; Jiang Qian; Haiping Hao; Albert S Jun Journal: Invest Ophthalmol Vis Sci Date: 2013-03-15 Impact factor: 4.799