Mechanisms of Apoptosis in Retinitis Pigmentosa
Mutations in humans are associated with several forms of inherited retinal dystrophies, such as Retinitis Pigmentosa which lead to retinal cell death and irreversible loss of vision. Genes involved in affected patients mainly encode proteins related to vision physiology including visual cycle and light-dependent phototransduction cascade. As reported in spontaneous and genetically engineered mouse models, apoptosis is a common fate in retinal degeneration, although the triggered signals to retinal apoptosis remain largely unraveled. Several studies highlighted that many of the molecular pathways involved in ocular diseases rely on caspase-dependent or -independent apoptotic mitochondrial pathway involving the Bcl-2 family of proteins. Anti-and pro-apoptotic Bcl-2 members are present in retinal tissues and are thought to play a role in the pathogenesis of several retinal disorders. Since almost no efficient treatments are available so far, it remains a great challenge to decipher the molecular pathways involved in retinal dystrophies and to develop alternative therapies to prevent or inhibit eye defect. Toward this goal, mutation-independent strategies such as molecular therapy provides promising and exciting approaches to deliver anti-apoptotic molecules targeting the Bcl-2 pathway through the use of cell permeable transport peptides. Modulation of common apoptotic signaling pathways may be of outstanding potential to target multiple retinal dystrophies regardless of the primary genetic defect.
- View record in Web of Science
Keywords: Retinal disease ; retinitis pigmentosa ; apoptosis ; Bcl-2 ; Bax ; therapy ; Photoreceptor Cell-Death ; Inherited Retinal Degeneration ; Lebers Congenital Amaurosis ; Rod Cgmp-Phosphodiesterase ; Rpe65(-/-) Mouse Model ; Bcl-2 Family-Members ; In-Vivo ; Beta-Subunit ; Gene-Therapy ; Slow Rds
Record created on 2010-11-30, modified on 2016-08-09