I. Abstract DONE The use of embryonic stem cells in research has been highly controversial.

Our idea focuses on the use induced pluripotent stem cells (iPS), cells taken from any tissue that has been genetically modified to behave like embryonic stem cells, instead. We will use the iPS cells to help replenish damaged or dying retinal pigmented epithelium cells (RPE). The RPE is a single-celled layer between the choroid and the retina, supports photoreceptors and has a self-contained immune system. It secretes substances to help build and sustain the choroid and the retina and is known to play a large role in light absorption. Degenerative eye diseases, such as macular degeneration or retinitis pigmentosa, often cause the RPE to decay, leading to irreversible vision loss. Macular degeneration alone affects over 30 million people worldwide. By using modified iPS cells to replace this layer, we will improve or even restore vision in those affected. II. Description: Present Technology (DONE): A human induced pluripotent stem cell (iPS) is a cell taken from any tissue that is genetically modified to behave like an embryonic stem cell in that they have the ability to differentiate into any adult cell type. This holds great promise for cellular therapy, as the stem cells may serve as a renewable resource which can be used to replenish other dead or dying cells and treat diseases. Recently, in an experiment conducted by researchers at the University of Oxford and National University Hospital of Singapore used stem cells (although not iPS cells) to regenerate photoreceptors on the retina. In another experiment, scientists at the Columbia University Medical Center successfully used iPS cell grafts to improve the sight of mouse models of retinitis pigmentosa.

For humans, research is still being conducted, thus not all of the side effects are known. As of now, many degenerative eye diseases, such as age-related macular degeneration or retinitis pigmentosa, do not have safe or effective treatments. Often, the degeneration of the patients sight can only be halted or slowed by using techniques such as surgery, which is risky since it is uncertain as to whether or not the patients body will reject the foreign tissue. The use of stem cells serves as a promising treatment for many incurable eye diseases, but significant technical difficulties still stand in the way of the breakthrough. Experiments are still being conducted on how to inject the cells into the patient without causing harm, keep the cells alive in the body after transplant, create sufficient quantities of tissue, and on the full implications of using induced pluripotent stems to replenish atrophied cells. History (DONE): To understand induced pluripotent cells, we must first examine the nature of embryonic stem cells, which are quite similar despite their different origins. Embryonic stem cells are taken from embryos, which are loosely defined as [unborn] babies in the early developmental stage...up to week eight from the time of fertilization (Biologyonline). Human embryonic stem cells were first isolated by James Thomson in 1998 at the University of Wisconsin. In November 2007, Shinya Yamanaka of Kyoto University and James Thomson of the University of Wisconsin-Madison independently publish papers on their discoveries of the induced pluripotent stem cells, which were created by inserting viruses into skin cells. The skin cells then acquired properties similar to that of the embryonic stem cells. On January 25, 2012, two people with eye degeneration were successfully treated with implants of retinal pigmented epithelial cells derived from

embryonic stem cells. However, the greatest breakthrough in terms of using iPS cells to cure degenerative eye diseases has been that of scientists at the Columbia University Medical Center, who successfully used iPS cell grafts to improve the sight of mouse models of retinitis pigmentosa. Future Technology: In the future, induced pluripotent cells will have the capability to fully integrate themselves into a human retina with no serious side effects, and have the ability to regenerate the light-sensitive retina. In addition, all the technology needed to produce enough quantities of tissue from induced pluripotent stem cells will be available and completely safe to use. Currently, iPS cell grafts have only been tested on mice models. However, hopefully someday the same idea may be applied to humans to cure degenerative eye diseases. Also, nanobots that are capable of handling the iPS cells will have to be invented and proven to be safe as well, since we are thinking of using injections with nanobots that will deliver the iPS cells into the eye, thus eliminating surgery, which is often costly and extremely risky. Breakthroughs DONE: Although induced pluripotent stem cells seem to be a simple treatment to diseases, the technology needed to use them to their greatest potential has not yet been perfected. They have been used successfully in mice, but have not been tested on human patients. Further experimentation, specifically a large-scale clinical trial, will lead to more conclusive results. To do this, patients with degenerative eye diseases who choose to receive this treatment of induced pluripotent cells will have their vision monitored and compared to others who choose to receive different or no treatment. Using a Snellen

Chart, we will monitor, in 2 week increments, the visual acuity of the subjects before, during, and after receiving treatment. It could not be a blinded experiment, due to ethical reasons, possibly affecting sample sizes. Because volunteers will have to be used, this project must last long enough to collect enough data that would be clinically significant. We must also stratify the data in order to gain insight into how the different treatments affect people of different ages, genders, and severity of disease. Blocking will be used to refer volunteers at specific treatment centers, which would control the factors of location and doctor prescribing treatment. To interpret the data, we will use statistical methods. First, we will measure the trend of the data from subjects receiving the iPS injection by calculating a correlation coefficient. This value will tell us approximately how much of the variation in the data can be attributed to the treatment. We expect at least a correlation coefficient of 0.75 to indicate a relationship between the variables vision (measured in magnification needed to obtain normal vision) and week of treatment. We will also calculate a correlation coefficient in the data from patients receiving other treatment. If the correlation coefficient is less than 0.15, we would suspect that the iPS treatment provides similar results in most cases. We will also find the best-fit line to both sets of data points. The slope of the line for iPS treatment should indicate a slope of about 0.05 to 0.125, or about a 50% increase in vision in 4-10 weeks. The slope of the best-fit line for other treatments should be lower, which would indicate that the other treatments are less effective. Although this experimental study would be expensive and time-consuming, the results could benefit the millions of people who suffer from degenerative eye diseases. Design Process DONE:

We had originally proposed to replace the cells with donated living cells, but then we realized the many complications. For example, the body may reject the donor cells, and it would be hard to completely replace cells with new ones, as the actual cells are microscopic and hard to handle. New nanotechnology would help solve this issue, but it is expensive and tedious. In addition, there would be no way to remove the dead cells without damaging the rest of the eye. Regarding the method used to deliver the cells, we were unsure that an injection would work, since it would require a numbing procedure, which would hinder the persons vision for up to 2 hours, and could cause infection. We considered both pills filled with nanobots that would deliver the cells and eye drops containing iPS cells that would seek out fluorescent markers already placed in the retina. However, we decided that the injection was still the best idea, since they directly affect the retina, as opposed to the eye drops or nanobots. We did some research about the injections into the eye and found that most procedures are very safe, with little to no major risks. Another problem we encountered was the design process. We had to research how to properly conduct a clinical trial and analyze the data. Also, at first, we were hesitant to write about the clinical trial at all, since it would have to include a comparison between the induced pluripotent stem cell therapy and embryonic stem cell therapy. We decided that we would only give the guidelines, and refrain from specifically mentioning embryonic stem cell therapy as an alternative treatment, since there is much controversy in that area. However, we did mention it as a concern in our consequence section. Consequences DONE: Using induced pluripotent stem cell therapy to restore the retinal pigment

epithelium will help improve vision in people with retinal degenerative diseases, which affects millions of people throughout the world. It minimizes the ethical problems associated with embryonic stem cells, and eliminates the need for donations from others, which requires immunosuppression drugs to prevent rejection. However, the use iPS cells in therapy brings up new concerns. They lack the proper evidence needed to guarantee their safety, since they are a new technology and have been shown to be similar to cancerous cells, so most people would be reluctant to take the risk in the clinical trials. Also, because further research is needed, the results from iPS cells must be compared to the data from using embryonic stem cells, which would mean destroying embryos to cultivate the stem cells. in addition, iPS cells have the potential to differentiate into a new embryo, which would result in a clone of the patient, again raising serious ethical issues. With all scientific breakthroughs come the questions that test our ethicality. However, we believe that perfecting induced pluripotent stem cell therapy, while creating new laws to adapt with the changing technology, will bring millions of people a vision of the future.