Stem Cells for Retinal Disease

Roger F. Steinert, MDIrving H. Leopold Professor and ChairProfessor of Biomedical EngineeringDirector, Gavin Herbert Eye InstituteUniversity of California, Irvine

Relevant Disclosures:None

Acknowledgment of UC Irvine Research Leader

Henry J. Klassen, MD, PhDAssociate Professor

Director, Stem Cell and Retinal Regeneration Program

Gavin Herbert Eye Institute

University of California, Irvine

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

Retinitis Pigmentosa (RP)

What the doctor sees What the patient sees

Retinal Degenerations: Symptoms Differ

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

Molecular analysis

RPCs

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 photoreceptorsBipolar cells

• 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

Vimentin

SOX2

Human RPCs

The cells are analyzed using molecular stem cell markers

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

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

Thank You!!