Discovery of Lens Epithelium-Derived Growth Factor (LEDGF)

In 1994 at the Center for Ophthalmic Research, Brigham and Women’s Hospital, Harvard Medical School, Dr. Singh and colleagues began with the hypothesis that LECs might contain a survival molecule. Drs. Shinohara, Chylack Jr. and Singh discovered a novel survival factor, Lens Epithelium-Derived Growth Factor (LEDGF; US patent: 67500520), that acts as a transcription factor. Dr. Singh has established that LEDGF, which stimulates the survival of cells including LECs, has the potential for enhancing cellular survival of LECs, the metabolic “engine” of the lens. His laboratory demonstrated that LEDGF is posttranslationally modified by Sumo1 (Small ubiquitin-like Modifier), and contains activating and repressing DNA binding modules which regulate survival gene(s) expression, including small heat shock proteins (hsps) and antioxidants genes depending upon cellular microenvironment and thus modify the physiology of cells to maintain cellular homeostasis. This is an important clue to the mechanisms by which expression or regulation of LEDGF is important for cell survival, and its aberrant expression may increase the risk of age-related cataract or other pathogenic disorders like cancer. Collectively, these works show great promise for both understanding the fundamental mechanisms of age-associated degenerative diseases including cataract, and application of LEDGF, a survival molecule, to the prevention of such disorders.