It is estimated that by 2020, over 450,000 Californians will suffer from vision loss or blindness due to the age-related macular degeneration (AMD), the most common retinal degenerative disease in the elderly. AMD is a progressive ocular disease of the part of the retina at the back of the eye, called the macula, which enables people to read, visualize faces, and drive. The disease initially causes distortion in central vision, and eventually leads to legal blindness.
A layer of cells at the back of the eye called the retinal pigment epithelium (RPE)provide support, protection, and nutrition to the light sensitive photoreceptors in the retina. The dysfunction and/or loss of these RPE cells play a critical role in the loss of the PR’s and hence the blindness in AMD. Effective treatment could be achieved by proper replacement of damaged RPE and retinal cells with healthy ones. RPE cells derived from human embryonic stem cells (hESC) are a potentially unlimited and robust source for regenerating RPE (hESC-RPE).
During the first year of our Disease Team Grant we have assembled a closely working team of interdisciplinary scientists and physician scientists at the University of Southern California (USC), Doheny Eye Institute (DEI), University of California Santa Barbara (UCSB), California Institute of Technology (Caltech), and City of Hope (COH). Our scientists work and meet together frequently to discuss progress and we have had 2 highly successful full-day retreats; one at USC and one at UCSB.
We are on track for each of the Year 1 proposed milestones. During the first year we have made a decision on final selection of hESC line; and have developed protocols for the generation and molecular and functional characterization of hESC-RPE and are transferring these protocols to our manufacturing and regulatory partners at City of Hope. COH has had onsite visits to learn protocols at UCSB and USC and we have had a day-long meeting at COH to further refine protocols and procedures. In collaboration with Caltech we have developed a non-biodegradable substrate on which these cells are grown and where they develop characteristics of mature RPE cells. Specialized surgical instruments have been developed at DEI and Caltech to implant the hESC cells grown on substrate under the retina. We have utilized sophisticated instrumentation to image the retina in live animals and have used these instruments to follow rats with progressive retinal degeneration before and after implantation of the hESC. We have demonstrated that hESC rescue the degeneration and integrate well into the host retina. Sections of these retinas are evaluated histologically at the microscopic level using sophisticated quantitative imaging techniques.
Our group is composed of unique multidisciplinary members who collectively have more than two decades of experience in efforts to restore sight to the blind as well as retinal cell transplantation and stem cell research. Our ultimate goal is to submit an Investigational New Drug (IND) Application to the Food and Drug Administration (FDA) by the end of the 4th year of the grant in order to get approval to conduct a clinical trial in patients at risk of vision loss due to AMD.