Final (Year 5)

Age-Related Macular Degeneration (AMD) is a devastating disease that can lead to severe vision impairment and blindness. Vision loss in AMD usually is after age 55 and affects almost 2 million Americans.
Vision is initiated by light striking and activating specific cells called photoreceptor cells of the neural retina within the eye. There is a small, specialized region in the central portion of the retina called the macula that is particularly important for central, sharp and color vision. It has a high percentage of photoreceptor cells called “cone cells” and it is this region that is most affected by AMD. Thus, with cone cell degeneration in AMD, a person loses their central, sharp vision, with color vision affected as well.
In the normal retina, photoreceptor cells are supported metabolically and structurally by a thin layer of cells next to them called Retinal Pigment Epithelial (RPE) Cells. Without these RPE cells, photoreceptor cells quickly degenerate and die. In AMD, it is thought that dysfunction of RPE cells is an early and critical sign of AMD. Thus, replacing dead or dying RPE cells in AMD could be a way to slow the disease process and even improve vision.

Our CIRM disease team which we call “The California Project to Cure Blindness (CPCB)” aims to treat AMD through replacement of these dysfunctional RPE cells with fresh RPE cells that will then keep photoreceptor cells alive and functioning. Because access to adult RPE cells is extremely limited, we produce RPE cells from human embryonic stem cells (hESCs). Through the work conducted by the CPCB team, we have been able to produce adult-like RPE cells that exhibit many characteristics of normal mature human RPE cells. These RPE cells are cultured on an ultrathin membrane that provides the RPE cells that proper signals for survival, polarization and function of the cells. The implant which includes the RPE cells and the membrane is delivered under the retina to support photoreceptors as a permanent implant.

In this last year, substantial progress has been made towards our goal of replenishing RPE cells in the AMD retina and restoring vision. During the last year, we have demonstrated the activity of the CPCB implant in slowing vision loss in a rodent model of retina degeneration. These studies, along with experiments performed in swine, showed that the implant could be safely delivered and maintained under the retina.

In parallel to these basic studies, we have advanced our strategies that will let us treat patients with AMD. A clinical protocol has been prepared and was submitted to the US FDA to gain their approval in order to start a Phase 1/2b early Clinical Trial. In summary, our CIRM grant has allowed us to develop a procedure that should let us treat severe vision loss in AMD. The data in animal studies has demonstrated the safety of the technique as well as the restoration of some functional vision in a model system. Hopefully, this will lead us to successful human clinical trials with sight restoration in currently untreatable cases of dry AMD.