Vision Loss

Coding Dimension ID: 
325
Coding Dimension path name: 
Vision Loss

The CIRM Human Pluripotent Stem Cell Biorepository – A Resource for Safe Storage and Distribution of High Quality iPSCs

Funding Type: 
hPSC Repository
Grant Number: 
IR1-06600
ICOC Funds Committed: 
$9 999 834
Disease Focus: 
Developmental Disorders
Heart Disease
Infectious Disease
Alzheimer's Disease
Neurological Disorders
Autism
Respiratory Disorders
Vision Loss
Stem Cell Use: 
iPS Cell
Cell Line Generation: 
iPS Cell
oldStatus: 
Active
Public Abstract: 
Critical to the long term success of the CIRM iPSC Initiative of generating and ensuring the availability of high quality disease-specific human IPSC lines is the establishment and successful operation of a biorepository with proven methods for quality control, safe storage and capabilities for worldwide distribution of high quality, highly-characterized iPSCs. Specifically the biorepository will be responsible for receipt, expansion, quality characterization, safe storage and distribution of human pluripotent stem cells generated by the CIRM stem cell initiative. This biobanking resource will ensure the availability of the highest quality hiPSC resources for researchers to use in disease modeling, target discovery and drug discovery and development for prevalent, genetically complex diseases.
Statement of Benefit to California: 
The generation of induced pluripotent stem cells (iPSCs) from patients and subsequently, the ability to differentiate these iPSCs into disease-relevant cell types holds great promise in facilitating the “disease-in-a-dish” approach for studying our understanding of the pathological mechanisms of human disease. iPSCs have already proven to be a useful model for several monogenic diseases such as Parkinson’s, Fragile X Syndrome, Schizophrenia, Spinal Muscular Atrophy, and inherited metabolic diseases such as 1-antitrypsin deficiency, familial hypercholesterolemia, and glycogen storage disease. In addition, the differentiated cells obtained from iPSCs represent a renewable, disease-relevant cell model for high-throughput drug screening and toxicology/safety assessment which will ultimately lead to the successful development of new therapeutic agents. iPSCs also hold great hope for advancing the use of live cells as therapies for correcting the physiological manifestations caused by disease or injury.

Generation and characterization of high-quality, footprint-free human induced pluripotent stem cell lines from 3,000 donors to investigate multigenic diseases

Funding Type: 
hiPSC Derivation
Grant Number: 
ID1-06557
ICOC Funds Committed: 
$16 000 000
Disease Focus: 
Developmental Disorders
Genetic Disorder
Heart Disease
Infectious Disease
Alzheimer's Disease
Neurological Disorders
Autism
Respiratory Disorders
Vision Loss
Cell Line Generation: 
iPS Cell
oldStatus: 
Active
Public Abstract: 
Induced pluripotent stem cells (iPSCs) have the potential to differentiate to nearly any cells of the body, thereby providing a new paradigm for studying normal and aberrant biological networks in nearly all stages of development. Donor-specific iPSCs and differentiated cells made from them can be used for basic and applied research, for developing better disease models, and for regenerative medicine involving novel cell therapies and tissue engineering platforms. When iPSCs are derived from a disease-carrying donor; the iPSC-derived differentiated cells may show the same disease phenotype as the donor, producing a very valuable cell type as a disease model. To facilitate wider access to large numbers of iPSCs in order to develop cures for polygenic diseases, we will use a an episomal reprogramming system to produce 3 well-characterized iPSC lines from each of 3,000 selected donors. These donors may express traits related to Alzheimer’s disease, autism spectrum disorders, autoimmune diseases, cardiovascular diseases, cerebral palsy, diabetes, or respiratory diseases. The footprint-free iPSCs will be derived from donor peripheral blood or skin biopsies. iPSCs made by this method have been thoroughly tested, routinely grown at large scale, and differentiated to produce cardiomyocytes, neurons, hepatocytes, and endothelial cells. The 9,000 iPSC lines developed in this proposal will be made widely available to stem cell researchers studying these often intractable diseases.
Statement of Benefit to California: 
Induced pluripotent stem cells (iPSCs) offer great promise to the large number of Californians suffering from often intractable polygenic diseases such as Alzheimer’s disease, autism spectrum disorders, autoimmune and cardiovascular diseases, diabetes, and respiratory disease. iPSCs can be generated from numerous adult tissues, including blood or skin, in 4–5 weeks and then differentiated to almost any desired terminal cell type. When iPSCs are derived from a disease-carrying donor, the iPSC-derived differentiated cells may show the same disease phenotype as the donor. In these cases, the cells will be useful for understanding disease biology and for screening drug candidates, and California researchers will benefit from access to a large, genetically diverse iPSC bank. The goal of this project is to reprogram 3,000 tissue samples from patients who have been diagnosed with various complex diseases and from healthy controls. These tissue samples will be used to generate fully characterized, high-quality iPSC lines that will be banked and made readily available to researchers for basic and clinical research. These efforts will ultimately lead to better medicines and/or cellular therapies to treat afflicted Californians. As iPSC research progresses to commercial development and clinical applications, more and more California patients will benefit and a substantial number of new jobs will be created in the state.

Restoring vision by sheet transplants of retinal progenitors and retinal pigment epithelium (RPE) derived from human embryonic stem cells (hESCs)

Funding Type: 
Early Translational IV
Grant Number: 
TR4-06648
ICOC Funds Committed: 
$4 318 439
Disease Focus: 
Vision Loss
Stem Cell Use: 
Embryonic Stem Cell
Cell Line Generation: 
Embryonic Stem Cell
oldStatus: 
Active
Public Abstract: 
There is currently no effective treatment to restore or improve vision for patients suffering from incurable blinding diseases such as dry age-related macular degeneration and retinitis pigmentosa, which need both new photoreceptors and retinal pigment epithelium. However, a unique method to transplant fetal retinal progenitor sheets together with its supporting retinal pigment epithelium (RPE) has been shown to improve vision in animal models of retinal degeneration and in patients. Differentiation of human embryonic stem cells (hESCs) into sheets of retinal progenitor tissue that contain photoreceptor progenitors and RPE cells could create an unlimited supply of donor tissue. Our lab has generated retinal progenitor tissue from hESCs in 3-D constructs (“layers”), and a new immunodeficient model of retinal degeneration. Recently, several laboratories have shown that hESCs can “self-assembly” into early stages of eye development and develop into laminated structures. The hypothesis of the proposed project then is that hESCs can be consistently differentiated into sheets of retinal tissue, which can restore visual responses after transplantation to a new immunodeficient rat model of retinal degeneration that does not reject human cells. In the final year, we will standardize methods to increase the production of these sheets in a way that complies to good manufacturing practice. This project will ultimately help to restore vision in patients suffering from retinal diseases.
Statement of Benefit to California: 
Retinal diseases reduce the quality of life of patients who suffer from vision loss and at significant cost to the health care system. Age-related macular degeneration (AMD) destroys the central vision and is the most common cause of blindness among people over 65. In 2010, AMD affected 2.1 % of the general population which means 2.1 million in the U.S. and about 240,000 in California, with these numbers projected to grow to 5 million (in the U.S.) in 2050 as the population ages. Ca. 20-35% of AMD cases develop irreversible geographic atrophy with local loss of RPE and photoreceptors in the macula. Another incurable disease, retinitis pigmentosa (RP) which is inherited (1:3500) and occurs in younger people, affects the light-sensing photoreceptors first, but also the supporting RPE layer beneath the retina following photoreceptor degeneration. Thus, both AMD and RP patients will need both new RPE and photoreceptors. The proposed replacement therapy is the only one that targets more mature disease stages of both AMD and RP, for which no other therapy exists. An effective treatment will keep afflicted individuals productive, enhance State tax revenues and defray the healthcare cost burden to taxpayers. It will also lead to robust industry developments in the fields of clinical transplantation, drug screening, and predictive toxicology, effectively leading to job creation and tax benefits to the State as a result of consumption of research and clinical goods and services.

Generation of fibroblast cell lines in patients with common blinding eye diseases

Funding Type: 
Tissue Collection for Disease Modeling
Grant Number: 
IT1-06601
ICOC Funds Committed: 
$1 034 452
Disease Focus: 
Vision Loss
oldStatus: 
Active
Public Abstract: 
Age-related macular degeneration (AMD), primary open-angle glaucoma (POAG), and proliferative diabetic retinopathy (PDR) are the major causes of irreversible vision loss worldwide. Although the exact causes and mechanisms of these diseases are not completely understood, it is known that genetic and environmental factors contribute to the development of these diseases. Recent scientific advances have enabled the reprogramming of already-differentiated tissues such as skin cells back to cells called induced pluripotent stem cells (iPSCs). iPSCs have the potential to be programmed into different cells in the eye, which are lost in degeneration. We therefore propose to obtain skin biopsies from patients with the above mentioned eye disease. The goals are to provide samples from a well-characterized patient population whose members exhibit the target eye diseases. Although there are animal models of eye diseases, retinal cells derived from iPSC will provide a better and faster way for disease modeling in the dish, novel tools for drug screening. The iPSC-derived retinal cells can also be used to replace degenerated or damaged retinal cells to restore vision for millions of patients, such as retinal pigment epithelium (RPE) cells to treat AMD and retinal ganglion cells to treat glaucoma.
Statement of Benefit to California: 
Blindness or impaired vision affects 3.3 million Americans ages 40 and over, or one in 28, according to a study sponsored by NIH. This figure is projected to reach 5.5 million by the year 2020. The rate of low vision and blindness increases significantly with age, particularly in people over age 65. California has the largest population in the United States. With the aging of the population, the number of Californians with age-related eye diseases is increasing, and vision loss is expected to remain a major public health and societal economic concern in addition to its substantial effect on individual living quality. Our proposed study of tissue collection from patients with major eye diseases will provide new means and materials to understand mechanisms of susceptibility to ocular diseases. It is innovative and promises a number of unique contributions to the field of regenerative medicine. By integration of clinical and genome-wide association datasets, we will be able to perform a comprehensive and coordinated study designed to identify and understand the complex interplay of genetic, developmental and environmental factors, and their contributions to the development and progression of major eye disorders. This should open a new avenue for future functional studies and could eventually help facilitate the prediction, development of improved treatment, and prevention of devastating blindness-causing diseases.

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