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Stem Cells for Retinal Disease. Roger F. Steinert, MD Irving H. Leopold Professor and Chair Professor of Biomedical Engineering Director, Gavin Herbert Eye Institute University of California, Irvine. Relevant Disclosures: None. Acknowledgment of UC Irvine Research Leader.
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Stem Cells for Retinal Disease Roger F. Steinert, MD Irving H. Leopold Professor and Chair Professor of Biomedical Engineering Director, Gavin Herbert Eye Institute University of California, Irvine Relevant Disclosures: None
Acknowledgment of UC Irvine Research Leader Henry J. Klassen, MD, PhD Associate Professor Director, Stem Cell and Retinal Regeneration Program Gavin Herbert Eye Institute University of California, Irvine
Further Acknowledgements • Harvard (SERI) • Michael Young • Caihui Jiang • Univ. of Missouri-Columbia • Randal Prather • Kristina Narfstrom • Duke Univ., NCSU • -Fulton Wong • -Robert Petters • Panum Institute, Copenhagen • Morten la Cour • Jens Kiilgaard • Maria Voss • University of Lund • Karin Warfvinge • UlricaEnglund Klassen Lab: UCI • UC Irvine • -Jing Yang • Gu Ping • Joann You • Jinmei Wang • Tianran Song • Steven Menges
Retinal Degenerations: Symptoms Differ Retinitis Pigmentosa(RP) What the doctor sees What the patient sees Age-Related Macular Degeneration (AMD)
Retinal Degenerations share a problem In both cases: loss of photoreceptors (rods/cones)
How to replace photoreceptors?Retinal Progenitor Cells (RPCs) • From the developing neural retina • RPCs are immature cells • Like stem cells, but self-renewal ends automatically • Perhaps why the retina loses the ability to regenerate? • Can be transplanted • Migrate • Integrate • Differentiate into retinal cells RPCs are the cells that make the retina, so they know what to do! RPCs in the lab
To first study the effect in mice need to make RPCs from green fluorescent mice RPCs Molecular analysis
Transplant to retina of blind mice Now look for the green fluorescent cells: Rod photoreceptors Bipolar cells These cells are from the transplant, yet look like normal retinal cells that have integrated into the right position.
GFP Rhodopsin Recoverin RPC transplantation has also been done in blind transgenic pigs, using cells from green fluorescent pigs New photoreceptors Green fluorescent pigs
Human RPCs have now been grown in the lab, using similar techniques SOX2 Human RPCs Vimentin The cells are analyzed using molecular stem cell markers
Human RPCs make new photoreceptors when transplanted to the retina of blind rodents From Jiang et al. Next step is to get FDA approval to test human RPCs in patients with retinal degenerative disease 11
Targeted Diseases • Retinal degenerations • Retinitis Pigmentosa (RP) and other dystrophies • Age-Related Macular Degeneration (AMD) • Retinal detachment • Optic nerve degenerations • Glaucoma and other optic neuropathies