Evaluation of silent information regulator T (SIRT) 1 and Forkhead Box O (FOXO) transcription factor 1 and 3a genes in g
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ORIGINAL ARTICLE
Evaluation of silent information regulator T (SIRT) 1 and Forkhead Box O (FOXO) transcription factor 1 and 3a genes in glaucoma Derya Yaman1 · Tamer Takmaz2 · Nilay Yüksel2 · Selin Akad Dinçer3 · Feride İffet Şahin3 Received: 5 July 2020 / Accepted: 6 November 2020 © Springer Nature B.V. 2020
Abstract Analysis of the reactive oxygen species (ROS)-detoxifying biomarkers may elucidate the mitochondrial dysfunction in glaucoma pathogenesis. Therefore, we purposed to investigate the effects of ROS-detoxifying molecules including Silent Information Regulator T1 (SIRT1) and Forkhead Box O 1 (FOXO1) and 3a (FOXO3a) transcription factors in patients with glaucoma. Our analyses included 20 eyes from patients with primary open-angle glaucoma (POAG) and 20 eyes from patients with pseudoexfoliation glaucoma (PXG) who were scheduled for trabeculectomy. After extraction of total RNA from trabecular meshwork tissue, we compared the levels of SIRT1, FOXO1and FOXO3a genes in the oxidative pathway with the level of glyceraldehyde-3 phosphate dehydrogenase (GAPDH), the reference gene, using real-time polymerase chain reaction. Relative gene expression was calculated using the threshold cycle (2−ΔΔCT) method. We observed similarly reduced expression levels of SIRT1, FOXO1, and FOXO3a genes versus GAPDH among patient groups (p = 0.40; p = 0.56; p = 0.35, respectively). This is the first study to identify the role of SIRT1 and FOXOs in human TM with glaucoma. Relative expression levels of SIRT1, FOXO1, and FOXO3a genes versus a control gene (GAPDH) were decreased in POAG and PXG groups. Our results show that SIRT1and FOXOs (1-3a) deserve special attention in the pathogenesis of glaucoma. Keywords SIRT1 · FOXO1 · FOXO3a · Primary open angle glaucoma · Pseudoexfoliation glaucoma
Introduction Glaucoma, characterized by accelerated retinal ganglion cell death, is a prominent neurodegenerative ocular disorder in aging populations worldwide [1]. Clinical findings of this heterogeneous group of the neurodegenerative disorders include increased intraocular pressure (IOP), optic disc excavation, thinning of the retinal nerve fiber layer (RNFL), and glaucomatous visual field defects. Of the various types of this complex neurodegenerative disease, primary openangle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG) are the most common types. POAG is characterized by the presence of glaucomatous optic neuropathy due to the * Derya Yaman [email protected] 1
Department of Ophthalmology, Kağızman State Hospital, Kars, Turkey
2
Department of Ophthalmology, Atatürk Training and Research Hospital, Ankara, Turkey
3
Department of Medical Genetics, Başkent University Faculty of Medicine, Ankara, Turkey
remodeling of the trabecular meshwork (TM) [2]. PXG, secondary open-angle glaucoma, is defined by the accumulation of fibrillary protein within the anterior chamber of the eye and other tissues of the body [3]. Clinically, the progression of the glaucomatous damage in PXG is faster than POAG. Although the clinic
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