Year 2

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 grant which we call The California Project to Cure Blindness 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 only very few RPE cells are present in a human eye, direct RPE transplantation would be very difficult so we rely on the use of human embryonic stem cells (hESCs). Through the work in our CIRM funded disease team grant we have been able to use a particular stem cell line and differentiate into adult-like RPE cells that exhibit many characteristics of normal mature human RPE cells. We believe that implanting these hESCs within the eye next to the retina could be of benefit in AMD in saving the photoreceptors.
Our technique is to not only implant the hESC derived RPE cells in the eye but to place them on a special ultrathin substrate platform that will maintain them in proper orientation next to the retina. Moreover, implantation can be done with hESC cells that had been allowed to differentiate in tissue culture prior to implantation, insuring that the implanted cells indeed express the characteristics of mature, functional RPE cells.
In this last year, substantial progress has been made in progressing to our goal of replenishing RPE cells in the AMD retina and restoring vision. First, a specific hESC line has been identified that will differentiate into cells that have many of the morphological and biochemical characteristics of normal adult RPE cells. Second, an appropriate material has been found that can act as a substratum (platform) that will support the RPE cells and allow them to function in a normal manner. Third, we have begun to demonstrated the safety of our procedure as well as its efficacy in slowing vision loss in a rodent model of retina degeneration. Fourth, we also have developed unique surgical techniques that will allow us to safely and effectively place the cells in the animal and ultimately human eyes.
In parallel to these basic studies, we are advancing our strategies that will let us treat human patients with AMD. Clinical protocols are being established that will be submitted to the US FDA to gain their approval in order to start phase 1 (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. Already, data at 6 months in animal studies has demonstrated the safety of the technique as well as the restoration of functional vision in a model system. Hopefully, this will lead us to a successful human clinical trial with sight restoration in currently untreatable cases of dry AMD.