title: Pathogenesis and treatments of TGFBI corneal dystrophies.
abstract: Transforming growth factor beta-induced (TGFBI) corneal dystrophies are a group of inherited progressive corneal diseases. Accumulation of transforming growth factor beta-induced protein (TGFBIp) is involved in the pathogenesis of TGFBI corneal dystrophies; however, the exact molecular mechanisms are not fully elucidated. In this review article, we summarize the current knowledge of TGFBI corneal dystrophies including clinical manifestations, epidemiology, most common and recently reported associated mutations for each disease, and treatment modalities. We review our current understanding of the molecular mechanisms of granular corneal dystrophy type 2 (GCD2) and studies of other TGFBI corneal dystrophies. In GCD2 corneal fibroblasts, alterations of morphological characteristics of corneal fibroblasts, increased susceptibility to intracellular oxidative stress, dysfunctional and fragmented mitochondria, defective autophagy, and alterations of cell cycle were observed. Other studies of mutated TGFBIp show changes in conformational structure, stability and proteolytic properties in lattice and granular corneal dystrophies. Future research should be directed toward elucidation of the biochemical mechanism of deposit formation, the relationship between the mutated TGFBIp and the other materials in the extracellular matrix, and the development of gene therapy and pharmaceutical agents.
authors.affiliation: Department of Ophthalmology, Ewha Womans University, School of Medicine, Seoul, South Korea.
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Han
authors.affiliation: Corneal Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Seung-il
authors.initials: SI
authors.lastname: Choi
authors.affiliation: Corneal Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea; Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Tae-im
authors.initials: TI
authors.lastname: Kim
authors.affiliation: Corneal Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Yong-sun
authors.initials: YS
authors.lastname: Maeng
authors.affiliation: Stulting Research Center, Woolfson Eye Institute, Atlanta, GA, USA.
authors.forename: R Doyle
authors.initials: RD
authors.lastname: Stulting
authors.affiliation: Corneal Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea; Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Ji
authors.affiliation: Corneal Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea; Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea; BK21 Plus Project for Medical Science and Severance Biomedical Science Institute, 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; D003315:Cornea / Q000378:metabolism; D003317:Corneal Dystrophies, Hereditary / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D005347:Fibroblasts / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D018384:Oxidative Stress / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta
keywords: Genetics; Granular corneal dystrophy type 2; Molecular mechanism; Transforming growth factor beta-induced corneal dystrophies; Transforming growth factor beta-induced protein