Looking Beneath the Surface

How did your studies lead you to ophthalmology, and to the ocular surface?

During my last year of medical school, I spoke to a resident two years my senior who had a passion for ophthalmology, and he strongly urged me to join his department – which I eventually did. As for choosing the ocular surface, that decision was simple. When I was working as a resident ophthalmologist, I saw so many devastating ocular surface diseases, and at the time we simply couldn’t treat them effectively. We would try, but the treatments and surgical procedures we used would often fail within three to six months. This inspired me to study that part of the eye, and to try and improve the options we had.

You’ve contributed greatly to the development of corneal stem cell theory. Can you tell us about that?

When I went to Harvard in 1979, there was no existing concept of corneal somatic stem cells, or of somatic stem cells at all – that came a few years later. My early work was somewhat related to the idea that stem cells were possibly located in the corneal limbal region. During my research, I discovered evidence of centripetal movement – the idea that corneal epithelial cells gradually move from the periphery to the center of the cornea, even during homoeostasis. This implied that some of the immature cells were located in a very peripheral area of the cornea, and opened up the possibility of stem cells in the limbal region. But at that time, there was no marker that could be used to pinpoint the cells, so it wasn’t possible to fully test the theory.

In the 1980s, there were many discoveries made that related to corneal epithelial stem cells. I think that was the time when the field really bloomed, and we acquired a lot of new knowledge on corneal epithelial biology, which could potentially be applied in the clinic.

How has ophthalmology changed since you first began working in the field?

When I started in 1974, we had so little compared with today: no posterior chamber IOLs, no LASIK, no anti-VEGF, the list goes on. Since then we’ve developed so many innovative instruments and pharmaceuticals to address unmet medical needs – the progress has been unmistakable. And although I believe we’ve made enormous progress in the last two decades with respect to corneal biology, when it comes to working towards ocular surface reconstruction using regenerative medicine, there’s still a long way to go – I think we really need another breakthrough.

Are you working with any companies to bring your own innovations to the market?

One idea we’re working on is the use of Rho-associated kinase inhibitor eyedrops that could be beneficial for corneal endothelial dysfunction. We have a patent and are collaborating with industry on this, but it’s an 
ongoing project.

I’ve also been focusing on new types of treatment for corneal disease, starting from the ocular surface, where we’ve been developing cultivated mucosal epithelial cell transplantation. This is now undergoing regulatory review by the Japanese Ministry of Health and Welfare.

We’ve also been working on the use of cultivated corneal endothelial cells derived from allogeneic donor cornea, and we’re trying to multiply these cultured endothelial cells and inject them into the anterior chamber. This is a totally new therapeutic approach and I believe it could be the future treatment of many corneal endothelial diseases, including Fuchs dystrophy, and some of the corneal dysfunction that occurs after many intraocular surgeries. We’ve done some clinical research on the direct injection of corneal endothelial cells, and this is showing promise. We hope that a clinical trial will be approved by the Japanese Ministry of Health next year, and our goal is to gain regulatory approval in my home country in the next two or three years, allowing us to potentially bring the treatment to other countries. We also hope to work with eye banks and companies – both profit or nonprofit – to try and take this forward, with the ultimate goal of developing effective solutions to the worldwide problem of corneal blindness.

Do you have any tips for working well with industry?

I haven’t found it a difficult thing to do – you need a good idea, and you need passion, and you should have a clear goal in mind. Then you need to find the right people at the company to talk to, and you’ll find that some of them will want to hear what you’re saying.

What advice would you give to the next generation of ophthalmologists?

I’d like to encourage them – I think the young have a lot of power, and some fantastic ideas too. If today’s young ophthalmologists put their minds to it, they can come up with new and improved treatments for both corneal and other diseases. So my advice would be: look at today’s unmet needs, and start creating the treatments of the future!