Inherited retinal degenerations result in loss of vision in patients as early as few months after birth. Retinitis Pigmentosa includes a group of such degenerations which run in families and can result in legal blindness by 40 years of age. Even though we know a number of gene defects which can cause these disorders, gene therapy is not available to help most of these patients. In this application, we are proposing to make new light-sensing cells called photoreceptors from stem cells to take up the function in the eye. We have shown that these cells once generated in the lab have the potential to restore some vision in mice with visual impairment secondary to inherited retinal degeneration. Another way these cells cells could also potentially help is by preventing the remaining cells in the eye from dying and thereby preserve native vision. Cellular replacement strategy could help all patients with vision disorder including age-related macular degeneration is used with the supporting pigment epithelial cells. The work proposed here will be carried out using cells that have been generated in clean facilities so that they can then be fast-tracked to the clinic.
Statement of Benefit to California:
Photoreceptor degenerations, including Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA), cause visual impairment for millions of people in the United States including a number of patients in the state of California as it is one of the most populous states in the US. RP and LCA encompass a group of retinal degeneration with a prevalence of up to 1 in 4000 and they often runs in families. Typical symptoms include night blindness followed by decreasing vision, and eventually legal blindness or, in many cases, complete blindness. RP is usually diagnosed in adolescents and young adults and most of these patients are legally blind by age 40. LCA on the other hand is much more severe affecting young children who often go blind very early in life. There are no effective forms of treatment for a majority of these patients. Thus, it results in a tremendous stress on the state of CA's resources. In addition, there is both monetary and psychological stress on the families especially as multiple family members are affected.
One way to potentially help these patients will be to replace the dead cells with new photoreceptors derived from stem cells. In this proposal, we will look into the feasibility of using pluripotent stem cells to generate the replacement photoreceptors and test their effectiveness in restoring vision. This proof of concept could eventually be applied to other retinal degenerative conditions like age-related macular degeneration in association with RPE.