Basic Biology IV
Stem Cell Use:
Embryonic Stem Cell
Cell Line Generation:
Inherited retinal degenerations result in visual loss in patients as early as in their adolescence. 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 by now a number of gene mutations which can cause these disorders, we do not understand how these mutations ultimately lead to loss of the cells. Recent advances in stem cell technologies now have provided us with the opportunity to gain a better understanding of the disorders. In this proposal, we plan to study the degenerative process by creating an eye-like structure in a dish using a combination of stem cell and bioengineering approaches. We plan to use 3D scaffolds to grow eye cells generated from pluripotent stem cells. We will directly compare normal retinal cells with cells derived from patients with Retinitis Pigmentosa. This approach will allow us to identify the processes that ultimately lead to the death of the photoreceptor cells int he eye and blindness. In the future, we could then extend this work to identify new drugs which will help halt or at least slow down the degeneration in these patients.
Statement of Benefit to California:
Photoreceptor degenerations, including Retinitis Pigmentosa (RP), cause visual impairment for millions of patients in the United States and a number of patients in the state of California being one of the most populous states in the US. RP encompasses a group of retinal degeneration with a prevalence of 1 in 4000 and 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. Most people with RP are legally blind by age 40. There are no effective forms of treatment for a majority of these patients. Thus results in a tremendous stress on the state of CA's resources. In addition, there is both monetary and psychological stress on the families esp. in cases of Retinitis Pigmentosa as multiple family members are affected. The only way to potentially help these patients will be to either replace the dead cells with new photoreceptors or find ways to better understand the degenerative process in order to identify novel drugs to delay the progression of degeneration. The proposed research in this application is to generate eye tissue in a dish from patients with severe forms of Retinitis Pigmentosa in order to gain a better understanding of the disease. This will in turn help us in the future to identify new drugs to delay or stop the visual loss and this will attract new biotechnology partners in the state of CA.
Inherited retinal degenerations result in visual loss in patients early in life. Retinitis Pigmentosa, a form of inherited retinal degeneration, affects thousands of patients in US and in the state of California. The second most common gene whose mutation results in retinitis pigmentosa is RP1. How mutation in the gene result in loss of vision is not completely clear and we are working of gaining a better understanding of this by creating a 3D artificial retina in a dish. This invloved using stem-cell derived eye cells grown on patterned articifical scaffolds. In our initial year of funding, we have improved our methodologies to make the various cells that make up the retina in the dish and are working on optimizing the generation of scaffolds. These scaffold will allow us to generated a retina, the light-sensing layer of the eye, in a dish. We have also over the course of the year generated stem cell lines using patient cells. Using the recent state-of-the-art technologies to convert patient cells to stem-cells, we have been able to convert blood cells to stem cells and then reconverted them to cells in the eye. We will now use these cells to better understand the degeneration and vision loss in the second year of the grant.
Inherited retinal degenerations result in visual loss in patients early in life. Retinitis Pigmentosa, a form of genetic disorder leading to vision loss, affects thousands of patients in US and in the state of California. The second most common gene whose mutation results in retinitis pigmentosa is RP1. How mutation in the gene result in loss of vision is not completely clear and we are working of gaining a better understanding of this by creating a 3D artificial retina in a dish. This involves using stem-cell derived eye cells grown on patterned artificial scaffolds. In our second year of funding, we have optimized our 3D bioengineered scaffold design to closely match the retina in the human eye. In addition, we have now been able to show that the stem cells generated from blood cells of patient with a defect in RP1 gene as well as an unaffected sibling can be converted to the various cells in the retina including the light sensing cells, These cells following placement in bioengineered 3D scaffolds allows alignment of the cells as if they are inside the eye. During the final year of funding, we will work on understanding why the light sensing cells undergo degeneration and if potential identify pathways which we can target to slow down the cells loss as well as test if restoring the gene function will allow to promote repair.