1. Stem Cells for Retinal Disease Roger F. Steinert, MDRoger F. Steinert, MD Irving H. Leopold Professor and ChairIrving H. Leopold Professor and Chair Professor of Biomedical EngineeringProfessor of Biomedical Engineering Director, Gavin Herbert Eye InstituteDirector, Gavin Herbert Eye Institute University of California, IrvineUniversity of California, Irvine Relevant Disclosures: None

2. 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

3. Further Acknowledgements UC Irvine -Jing Yang –Gu Ping –Joann You –Jinmei Wang –Tianran Song –Steven Menges 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 –Ulrica Englund Klassen Lab: UCI Harvard (SERI) –Michael Young –Caihui Jiang

4. Retinitis Pigmentosa (RP) What the doctor seesWhat the patient sees Retinal Degenerations: Symptoms Differ Age-Related Macular Degeneration (AMD)

5. Retinal Degenerations share a problem In both cases: loss of photoreceptors (rods/cones)

6. 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

7. To first study the effect in mice need to make RPCs from green fluorescent mice Molecular analysis   RPCs

8. Transplant to retina of blind mice Now look for the green fluorescent cells: These cells are from the transplant, yet look like normal retinal cells that have integrated into the right position. Rod photoreceptors Bipolar cells

9. GFP Rhodopsin Recoverin RPC transplantation has also been done in blind transgenic pigs, using cells from green fluorescent pigs New photoreceptors Green fluorescent pigs

10. Human RPCs have now been grown in the lab, using similar techniques Vimentin SOX2  Human RPCs The cells are analyzed using molecular stem cell markers

11. 11 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

12. 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

13. Thank You!!