Anti-TGFBI monoclonal antibody, clone l2I23

Type 2 granular corneal dystrophy (GCD2) is caused by point mutation R124H in the transforming growth factor-beta-induced gene (TGFBI) and is characterized by age-dependent progression of corneal deposits. Mitochondrial features in heterozygous GCD2 and normal corneal tissues was evaluated using electron microscopy. Primary corneal fibroblasts of homozygous and normal corneas were cultured to passage 4 or 8. Keratocytes of normal corneal tissue are narrow, and details of their intracellular organelles are difficult to distinguish. Keratocytes of heterozygous GCD2 tissues exhibited many degenerative mitochondria. MitoTracker and cytochrome c staining demonstrated increased mitochondrial activity in mutated cells at early passages. Decreases in depolarized mitochondria, cellular proliferation, and expression of complexes I to V and increases in apoptotic change were observed in late-passage mutant fibroblasts. PGC-1 alpha, ANT-1, p-Akt, and p-mTOR but not NF-kappa B expression demonstrated a passage-dependent decrease in all cells. Increased passage- or mutation-related intracellular reactive oxygen species and delayed proliferation of methanethiosulfonate (MTS) were recovered using application of antioxidant butylated hydroxyanisole. Mitochondrial features and function were altered in mutated GCD2 keratocytes, in particular in older cells. Alteration of mitochondrial function is critical for understanding the pathogenesis of GCD2. (Am J Pathol 2011, 179:684-692; DOI: 10.1016/j.ajpath.2011.04.005)

Purpose: This report suggests how corneal dystrophies (CDs) should be diagnosed at the slit lamp and specifies the new (ICD)-D-3 classification of CDs in 2015 which incorporates new information. Methods: (ICD)-D-3 reviewed all peer-reviewed articles on CDs 2008 to 6/2014. Corneal dystrophy templates and anatomic classifications were updated. Results: To detect landmarks for correct classification of CDs, opacity patterns and opacity units are determined at the slit lamp. Opacity patterns are described as (1) horizontal extension, (2) vertical extension ("depth") and clarity of the (3) cornea in between. Horizontal extension is assessed using a broad beam, vertical extension using a bright, thin slit lamp beam in high magnification. For assessment of opacity units, examination using retroillumination with dilated pupil is indispensable! This is especially true for epithelial and endothelial CDs. With a better review of the cellular origin of CDs, a new anatomic classification is proposed: 1. epithelial and subepithelial; 2. epithelial-stromal transforming growth factor beta-induced (TGFBI); 3. stromal; 4. endothelial dystrophies. Epithelial recurrent erosion dystrophies include three epithelial dystrophies (Franceschetti CD, dystrophia Smolandiensis, and dystrophia Helsinglandica) and are differentiated against TGFBI dystrophies, also associated with recurrent epithelial erosion. The chromosome locus of Thiel-Behnke CD is only located on 5q31. The entity previously called Thiel-Behnke on chromosome 10q24 may be a unique corneal dystrophy. Congenital hereditary endothelial dystrophy (CHED, formerly CHED2) is an autosomal recessive disorder. The autosomal dominant inherited CHED (formerly CHED1) is insufficiently distinct to be a unique entity and most cases appear to be similar to other reported dystrophies, particularly posterior polymorphous corneal dystrophy (PPCD). Conclusions: The 2015 revision of (ICD)-D-3 classification includes an updated anatomic classification more accurately describing TGFBI dystrophies to affect multiple layers. Some entities, e.g., Grayson Wilbrandt, Meretoja syndrome, and CHED2 are removed. All authors and reviewers should adhere to this classification of CDs!