Using stem cells to understand blinding eye diseases Dr Duncan Crombie Neuroregeneration Research We conduct eye research with real-life impact. We are unravelling the causes of diseases, preventing blindness through earlier diagnosis and better treatments, and restoring sight. We are closely affiliated with the University of Melbourne Department of Ophthalmology, and are co-located with the Department at the Royal Victorian Eye and Ear Hospital. This three-way partnership between CERA, the University and the Hospital, is key to the successful translation of our research from the bench to the bedside. Our ultimate goal is to find solutions for the three major blinding eye diseases that affect Australians – macular degeneration; glaucoma and diabetic eye disease – and to pioneer vision regeneration programs to give hope to people who have lost their sight.

Pluripotent Stem Cells

Stem cells can be guided to become cardiomyocytes (heart cells)

…Or neurons (nerve cells)

Pluripotent stem cells can become cells of the retina Retinal ganglion cells (RGCs) Gill et al Scientific Reports 2016 Retinal pigment epithelial cells (RPE cells) Crombie et al Drug Disc Today: Dis Mod 2016

Pluripotent stem cells can become cells of the retina and used to study diseases of the eye Glaucoma, Leber’s Hereditary Optic Neuropathy Retinitis pigmentosa Age-related macular degeneration (AMD)

Where is the research heading next? In both groups, NR or RPE selective, we could see neural rosette formation and stratification in the spheres by day 30. After 40 days, there were more clear stratified “optic cup-like” structures

Retinal Organoids In both groups, NR or RPE selective, we could see neural rosette formation and stratification in the spheres by day 30. After 40 days, there were more clear stratified “optic cup-like” structures Adapted from http://www.bem.fi/book/28/28.htm

Advancing stem cell culture - Pluripotent Stem Cells – 12 years ago Manual Passaging 2 full-time researchers 8 stem cell lines

Pluripotent Stem Cells – Today, Automated Stem Cell Culture Automated passaging and feeding 1 PhD candidate with support from the team >300 stem cell lines and counting; including from 150 glaucoma patients

Using stem cells to understand eye disease – finding phenotypes Davidson et al, 2014

Acknowledgements Neuroregeneration Alice Pébay Maciej Daniszewski Centre for Eye Research Australia Ophthalmology, University of Melbourne Neuroregeneration Alice Pébay Maciej Daniszewski Alison Conquest Katie Gill Damian Hernandez Tejal Kulkarni Grace Lidgerwood Louise Rooney Sophie Chevalier Cellular Reprogramming Raymond Wong Clinical Genetics Alex Hewitt Helena Liang Lisa Kearns Sandra Staffieri Linda Clarke Elisabeth De Smit Fan Li Tristan McCaughey Sandy Hung University of Tasmania Anthony Cook James Vickers Mathew Summers Johns Hopkins University Donald Zack Valentin M. Sluch Xitiz Chamling Flinders University Jamie Craig University of Queensland Joseph Powell CSIRO Andrew Laslett Hun Chy University of Western Australia David Mackey Funding Clemenger Foundation National Health & Medical Research Council Ophthalmic Research Institute of Australia Retina Australia