Hurvitz Brain Sciences Program

Education:

• BSc in Anatomy and Cell Biology, 2005, McGill University, Canada
• PhD in Neurological Sciences, 2011, Montreal Neurological Institute, McGill University, Canada
• MDCM, 2013, Faculty of Medicine, McGill University, Canada
• Ophthalmology Residency, 2018, Department of Ophthalmology and Vision Sciences, University of Toronto, Canada
• Fellow of the Royal College of Physicians and Surgeons of Canada, 2018
• Clinical-Research Fellowship in Cornea, External Eye Diseases and Refractive Surgery, 2020, Massachusetts Eye and Ear, Harvard Medical School, USA

Appointments and Affiliations:

• Clinician-Scientist, Biological Sciences Platform, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute
• Cornea Specialist, Sunnybrook Health Science Centre
• Assistant Professor, Department of Ophthalmology and Vision Sciences, University of Toronto
• Assistant Professor, Department of Laboratory Medicine and Pathobiology
• Associate Graduate Faculty, Department of Laboratory Medicine and Pathobiology

Research Foci:

• Fuchs endothelial corneal dystrophy
• Regeneration of the corneal endothelium
• Endothelial to mesenchymal transition of the corneal endothelium
• Cellular migration of corneal endothelial cells
• Genetics of Fuchs endothelial corneal dystrophy

Research Summary:

The corneal endothelium (CE) is the inner layer of the cornea that plays a key role in maintaining the clarity of the cornea, and thus keeping vision clear. The CE is composed of corneal endothelial cells (CECs) that rest on a specialized membrane called Descemet’s membrane. Damage to these CECs results in a decreased ability to pump fluid out of the cornea, which leads to fluid accumulation in the cornea, reduction in vision, and eye pain. Fuchs endothelial corneal dystrophy (FECD) is the most common disease of the CE affecting approximately 4 per cent of the population over the age of 40 years, and is also the leading indication for corneal transplantation worldwide. FECD is a typically age-related late-onset disease with a female predilection characterized by CEC death and the formation of abnormal collagen deposits called guttae. There are limited options for the treatment of FECD, which usually involves surgical intervention with a corneal transplant. Recently, a surgical technique termed Descemet’s Stripping Only (DSO) has been developed whereby the abnormal central CE is removed without replacing it with a transplant. The cornea clears as result of the healthier and normal-appearing CECs migrating from the periphery towards the center of the cornea. However, despite the importance of cell migration in DSO and FECD, little is known about what controls this process.

Dr. Ong Tone’s research interests include understanding the mechanisms that regulate and maintain a normal and healthy CE, and investigating diseases such as FECD. Dr. Ong Tone’s research aims to understand what causes FECD, and what regulates CEC migration in FECD. To answer these questions, he has developed a novel live imaging technique to observe the movement of CECs from tissues that have been collected from FECD patients during corneal transplant surgery. Furthermore, Dr. Ong Tone tries to understand what makes CEC behaviour different between patients including genetics (TCF4 genetic mutation), biological sex, and other cell signalling pathways such as the endothelial-to-mesenchymal transition pathway. Overall, with a greater understanding of FECD pathogenesis and CEC biology, potential new therapies and regenerative treatments can be developed aimed at curing FECD and other causes of corneal blindness.

Selected Publications:

See current publications list at PubMed.

1. Ong Tone S, Wylegala A, Böhm M, Melangath, G, Deshpande, N, Jurkunas UV. Increased corneal endothelial cell migration in Fuchs endothelial corneal dystrophy: A live cell imaging study.Ophthalmology Science. 2021 March 9 https://doi.org/10.1016/j.xops.2021.100006
2. Ong Tone S, Kocaba V, Böhm M, Wylegala A, White TL, Jurkunas UV. Fuchs endothelial corneal dystrophy: The vicious cycle of Fuchs pathogenesis. Prog Retin Eye Res. 2020 May 8:100863. doi: 10.1016/j.preteyeres.2020.100863. Epub ahead of print. PMID: 32438095; PMCID: PMC7648733
3. Ong Tone S, Wylegala A, Boehm M, Melangath G, Jurkunas UV; Increased corneal endothelial cell migration in Fuchs endothelial corneal dystrophy, with or without TCF4 repeat expansion. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1188
4. Liu C, Miyajima T, Melangath G, Miyai T, Vasanth S, Deshpande N, Kumar V, Ong Tone S, Gupta R, Zhu S, Vojnovic D, Chen Y, Rogan EG, Mondal B, Zahid M, Jurkunas UV. Ultraviolet A light induces DNA damage and estrogen-DNA adducts in Fuchs endothelial corneal dystrophy causing females to be more affected. Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):573-583. doi: 10.1073/pnas.1912546116. Epub 2019 Dec 18. PMID: 31852820; PMCID: PMC6955350.
5. Ong Tone S, Bruha MJ, Böhm M, Prescott C, Jurkunas U. Regional variability in corneal endothelial cell density between guttae and non-guttae areas in Fuchs endothelial corneal dystrophy. Can J Ophthalmol. 2019 Oct;54(5):570-576. doi: 10.1016/j.jcjo.2018.12.009. Epub 2019 Jun 17. PMID: 31564347; PMCID: PMC6776238.
6. Ong Tone S, Melangath G, Deshpande N, Jurkunas UV; Immortalization of Fuchs Endothelial Corneal Dystrophy (FECD) Corneal Endothelial Cells (CEnC) Retains TCF4 Repeat Expansion. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2174.