Pathogenesis and treatments of TGFBI corneal dystrophies

• Published in: Progress in retinal and eye research Vol. 50; pp. 67 - 88
• Main Authors: Han, Kyung Eun, Choi, Seung-il, Kim, Tae-im, Maeng, Yong-Sun, Stulting, R. Doyle, Ji, Yong Woo, Kim, Eung Kweon
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2016
• Subjects: Autophagy - physiology; Cornea - metabolism; Corneal Dystrophies, Hereditary - etiology; Corneal Dystrophies, Hereditary - genetics; Corneal Dystrophies, Hereditary - metabolism; Corneal Dystrophies, Hereditary - therapy; Fibroblasts - pathology; Genetic Predisposition to Disease; Genetics; Granular corneal dystrophy type 2; Humans; Molecular mechanism; Mutation; Oxidative Stress - physiology; Transforming Growth Factor beta - metabolism; Transforming growth factor beta-induced corneal dystrophies; Transforming growth factor beta-induced protein; Molecular mechanism; PTK; PRK; ALKP; TGFBIp; mTOR; Genetics; FAS1; UPS; Transforming growth factor beta-induced corneal dystrophies; KE; WT; Transforming growth factor beta-induced protein; MMC; DALK; BAC; GCD1; TBCD; LASEK; GCD2; LCD; LASIK; ECM; RGD; PKP; FD-OCT; RBCD; ROS; RK; Granular corneal dystrophy type 2; TGFBI
• ISSN: 1350-9462; 1873-1635
• DOI: 10.1016/j.preteyeres.2015.11.002

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.