title: Autophagy in granular corneal dystrophy type 2.
abstract: Autophagy is a lysosomal degradative process that is essential for cellular homeostasis and metabolic stress adaptation. Defective autophagy is involved in the pathogenesis of many diseases including granular corneal dystrophy type 2 (GCD2). GCD2 is an autosomal dominant disorder caused by substitution of histidine for arginine at codon 124 (R124H) in the transforming growth factor β-induced gene (TGFBI) on chromosome 5q31. Transforming growth factor β-induced protein (TGFBIp) is degraded by autophagy, but mutant-TGFBIp accumulates in autophagosomes and/or lysosomes, despite significant activation of basal autophagy, in GCD2 corneal fibroblasts. Furthermore, inhibition of autophagy induces cell death of GCD2 corneal fibroblasts through active caspase-3. As there is currently no pharmacological treatment for GCD2, development of novel therapies is required. A potential strategy for preventing cytoplasmic accumulation of mutant-TGFBIp in GCD2 corneal fibroblasts is to enhance mutant-TGFBIp degradation. This could be achieved by activation of the autophagic pathway. Here, we will consider the role and the potential therapeutic benefits of autophagy in GCD2, with focus on TGFBIp degradation, in light of the recently established role of autophagy in protein degradation.
authors.affiliation: The Institute of Vision Research, Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Seung-Il
authors.initials: SI
authors.lastname: Choi
authors.affiliation: The Institute of Vision Research, Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, South Korea; Severance Biomedical Science Institute, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: eungkkim@yuhs.ac.
authors.forename: Eung Kweon
authors.initials: EK
authors.lastname: Kim
mesh_terms: D001343:Autophagy / Q000502:physiology*; D003317:Corneal Dystrophies, Hereditary / Q000209:etiology / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008247:Lysosomes; D059748:Proteolysis; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein
keywords: Autophagy; Corneal fibroblasts; ECM endocytosis; GCD2; TGFBIp