Diana Katsman, M.D.

UCLA - New Investigator

Projetc Title: “Activation of the retina's regenerative potential by stem cell-derived microvesicles."

 

Retinal degenerative diseases including retinitis pigmentosa, Usher syndrome, Stargardt’s disease, and macular degeneration are among the leading causes of irreversible blindness in the world.  Recent advances in retinal regenerative research and stem cell transplantation have been promising.  Muller cells, the cells found throughout retinal layers and until recently known primarily for their scaffolding and supporting roles in the retina are emerging as good candidates for retinal progenitor cells (RPCs). These cells have the potential to regenerate into multiple cell types of the retina, including retinal pigmented epithelium and rod and cone photoreceptors, the cells that deteriorate in many types of retinal degenerative diseases. While Muller cells are activated in the injured retina with some regenerative success, functional retinal recovery has not yet been demonstrated.  Currently, a novel concept of employing stem cell-derived factors to activate the intrinsic capacity of tissues to regenerate has shown promising results in blood, liver, and lung tissues.  Many cell types, including stem cells, have been found to release microvesicles (MVs).  These are small vesicles that contain molecules important in cell-cell communication, cellular regeneration and remodeling.  MVs are likely to influence the fate of surrounding cells.  It has been shown that stem cell-derived MVs (ESMVs) carry genetic information that dictates early development of cells.  Moreover, ESMVs have been shown to enhance survival of adult blood lineage progenitor cells.  We hypothesize that by transfer of stem cell-specific molecules, ESMVs may facilitate the activation of adult inactive progenitor cells, which in turn will stimulate regeneration by repopulating and repairing the damaged tissue.  This activation/regeneration paradigm would be particularly well suited for retinal regenerative therapy development.  Indeed, retinal degenerative diseases can be diagnosed at early stages, the retina is easily accessible for factor delivery and transplantation by minimally invasive techniques, and assessment of functional recovery is possible by molecular biology, biochemistry, and physiology methods.