The National Eye Institute (NEI) has awarded grants to five multi-disciplinary teams to develop new disease models for a range of eye conditions. The program is part of the NEI Audacious Goals Initiative (AGI) for Regenerative Medicine. The AGI will encourage new treatments for glaucoma, age-related macular degeneration, retinitis pigmentosa, and other degenerative eye diseases. The new models will enable researchers to test novel regenerative therapies, and help transition them to the clinic.

Scientists use disease models to develop new treatments. From cell or animal models of eye diseases, researchers can learn the root cause of disease, study the changes that occur to eye tissues as the disease progresses, and test potential therapies.

New and emerging treatments, like gene therapy or stem cell-based tissue-replacement, also require novel surgical techniques and ways to understand how well therapy is working before being tested in humans. Models that closely match human biology and disease will help scientists test new methods to preserve and restore sight. Key models that mimic important aspects of human physiology, such as light-sensing cells, and eye-brain pathway.

Retinal Disease Models for Translational Photoreceptor Replacement

Principal investigators: John H. Wolfe, Children’s Hospital of Philadelphia; William A. Beltran, University of Pennsylvania; David M. Gamm, University of Wisconsin

Wolfe, Beltran, Gamm and their colleagues are using animal models to develop gene therapies for degenerative eye diseases, including retinitis pigmentosa. Current gene therapies can only save regions of the retina that retain living cells. They cannot restore function to damaged areas of the retina.

Their research will study how to implant replacement adult stem cell-derived light-sensing photoreceptor cells into these damaged retinal regions. The models will enable them to test surgical techniques, evaluate how well the replacement cells are working, and determine whether the treatment restores vision.

Retinal Ganglion Cell Replacement in Optic Neuropathies

Principal investigators: Jeffrey L. Goldberg, Stanford University; David J. Calkins, Vanderbilt University; Thomas A. Reh, University of Washington; Donald J. Zack, Johns Hopkins University

This team is generating a new animal model system to study how to place new retinal ganglion cells into the eye and guide the cells’ nerve fibers to appropriate regions of the brain. Success would constitute overcoming a major hurdle in the development of treatments for vision loss due to glaucoma and other optic neuropathies.

Models of Cone Disorders and Other Heritable Retinal Diseases

Principal investigators: Jeffrey A. Rogers, Rui Chen, and John T. Stout, Baylor College of Medicine; Sara M. Thomasy and Ala Moshiri, University of California Davis, California National Primate Research Center (CNPRC)

Rogers and colleagues are exploring cases where animals have naturally occurring ocular diseases. The team will use these animal models to help develop therapies for diseases that cause the loss of cone photoreceptors—cells in the retina that detect color.

The investigators at the CNPRC have discovered several animals with naturally occurring visual impairment and cone dysfunction. The Baylor team has identified specific mutations in those impaired animals in genes like PDE6C that in humans cause cone photoreceptor degeneration. The project will characterize retinal degeneration in these animals, explore ways to replace cone photoreceptors and restore visual function, and survey additional animals to identify other valuable naturally occurring disease models.

Developing Cone-Dominant Retinal Disease Models as a Resource for Translational Vision Research

Principal investigators: Joseph Carroll, Medical College of Wisconsin; Jacque Duncan, University of California San Francisco

Carroll and colleagues are pursuing new small animal models that will enable translational research into diseases that affect cone photoreceptors. Their team is working with two small mammals with high cone density: the 13-lined ground squirrel and the tree shrew.

Retinal Ganglion Cell Replacement in Clinically Relevant Models of Optic Neuropathy

Principal investigators: Tonia Rex, Vanderbilt University Medical Center; Brian Samuels, the University of Alabama at Birmingham; Petr Baranov, Schepens Eye Research Institute of Mass. Eye and Ear, Harvard Medical School

Rex and colleagues are developing optic cup organoids – lab-grown tissues with the potential to regrow retinal ganglion cells. Using tree shrews, the team will first characterize what happens after optic nerve trauma or glaucoma in these animals. They will then test how to transplant retinal ganglion cells, isolated from stem cell-derived organoids.

Learn more about Audacious Goal Initiative.
Source: News Brief, NEI, October 2018