Regeneration of functional retinas: treatment with human embryonic stem cell microvesicles

Funding Type: 
Early Translational IV
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Our proposal is unique in that having characterized how stem cells influence their environment by talking to each other and to other cell types, we can now successfully harvest their communication signals, called microvesicles, and may safely and effectively treat retinal diseases with them. The leading causes of new blindness in the developed world are retinal diseases. We will not be transplanting stem cells, but harvesting their regenerative signal and treating afflicted eyes with the signal alone. We will focus on retinitis pigmentosa, cone- and cone-rod dystrophies but our novel regenerative strategy could potentially be used to treat patients across the entire spectrum of blinding diseases, including retinopathy of prematurity and Stargardt disease in children, diabetic retinopathy and myopic macular degeneration in adults, and AMD and glaucoma in seniors. By reversing disease-based retinal damage we will reduce suffering and vision loss. Hypothetically this treatment may be much safer than stem cell transplantation given the decreased risk of immune rejection or tumor formation. We will study human stem cell-derived microvesicles effects on a mouse model of acute retinal injury and determine the % recovery of damaged cells and functional retina. We will then assess the treatment in the rd1 mouse, a model of retinitis pigmentosa that rapidly loses all photoreceptors, to confirm the microvesicles’ capacity for regeneration of most retinal degenerations.

Statement of Benefit to California: 

Retinal diseases are the leading causes of new blindness in Californians. This proposal introduces a novel, regenerative treatment strategy with the potential to safely and effectively treat patients with retinal diseases. Specific examples of prevalent retinal disease include retinopathy of prematurity, Stargardt & retinitis pigmentosa in the pediatric age, diabetic retinopathy & myopic macular degeneration in working age Californians, and AMD & glaucoma in senior Californians. A number of orphan retinal diseases are also potential targets. A therapeutic approach that could treat and even reverse disease-based retinal damage would provide an almost unimaginable reduction in suffering. In addition, the ongoing care and extensive adaptive measures necessitated by the current lack of successful therapeutic modalities are an enormous burden on the pocketbooks of both the State and affected individuals. Recovery of the damaged retina would offer tremendous functional and fiscal benefits to California and its residents.

Further, the innovative approaches described in the project herein would benefit California because they could have application not only for the treatment of diseased eyes but also for other diseases. When this project enters the clinical phase it will likely attract new biotechnology investment in California and funding by the federal government. This proposal well represents the broad mission of CIRM and the objective of the Early Translational IV Awards program.