A joint initiative by the ‘Gateway to Vision research (vision-research.eu)’ and the European Vision Institute EEIG
What are the main topics you want to address within the coming years?
Gene therapy of inherited retinal degeneration due to mutations in genes expressed in photoreceptor cells. In particular those diseases due to mutations in genes whose size prevents the efficient use of vectors like AAV. I would like to be able to overcome this challenge in the lab and then move this to the clinic.
For me a key issue is to find new ways of integrating the huge amount of data now available to drive the next level of understanding of pathogenesis (particularly in retinal disease) and to help inform clinical decision-making in ophthalmology. If we succeed in this we will have developed an approach that will find utility in solving the problems of complex age-related disorders of the eye.
What is the personal motivation of your work?
The possibility to answer very important scientific questions and, by overcoming major scientific challenges, to provide benefit to patients with blinding conditions.
Prior to my current position as chief of a university eye clinic, I co-founded and managed a private clinical and research institute in Zurich, Switzerland. Instead of focusing only on patient care, the institute partners established a method to treat corneal dystrophies from the pre-clinical studies to an internationally established procedure.
Therefore, my motivation to transition back to a university setting from private practice is to repeat this success on a grander scale. With the manpower and resources available only at a university, I am highly motivated to pursue this vision.
Several factors come together to drive my enthusiasm for this approach. As a pathologist, I am always intrigued to understand how all the elements we see in a single case come together to make a story. But more importantly, we would be in a much stronger position to take novel therapies forward successfully into clinical use if we had tools that allowed us to appreciate the complexity of the systems we seek to modify. There is also an issue that only with sophisticated models of disease will we be able to take the personalized medicine agenda forward as powerfully as possible.
Science is risky - an intellectual and practical journey into the unknown. Whenever we leave our textbooks, we leave home, traveling into the unknown. Whereas scientists and doctors of previous centuries would travel the world to find new islands, continents, plants as well as treatments and drugs thereby risking their lives and health, we are now exploring molecular world and oceans of the unknown. The eye is the most important sensory organ to connect us with the outside world and visual impairment a very frequent fate. As such, exploring and finding ways to save the eye from getting blind has a meaning that motivates me to contribute to this.
There is something else: Science is adventure - including the risk to fail. But eye research as well as new treatment introduced as a consequence of research is successful – more than in other fields for example such as cancer. Our community pioneered successful gene therapy, we are now entering cell therapy. So the adventure pays off for us, for the young people to join us and more importantly for those that are at risk to loose their vision.
How would you describe the present situation of Vision Research and Ophthalmology on the national, European and international level?
I think this is an exciting time for those working in the field of genetic ocular diseases, whether they are basic scientists like me or ophthalmologists dealing directly with patients. Thanks to major advancements in the field of molecular diagnosis (next generation sequencing) and cell and gene therapy I think that the time of “I don’t know if and when I can give you an answer regarding your genetic form of blindness” or “ you will eventually go blind, there is nothing we can really do” hopefully will come to an end in the next decade.
Ophthalmology seems again a frontier for development of new therapeutic approaches and new applications for compounds developed within other specialties.
The gap between clinical and laboratories sciences inhibits translational research and is a global problem for the advancement of vision research as a whole. More specifically, laboratory scientists often have only partial knowledge about the clinical open questions, and the clinician is generally not informed about the possibilities that laboratory sciences offer. A person that unites the possibilities of both sciences would be an MDPhD.
To further clarify, the MDPhD would serve to close the gap or rather a liaison between the two sciences. The actual laboratory PhD scientist would then do the scientific development, and the clinical scientist would cover the clinical investigations.
National MDPhD programs exist is most countries, but the main responsibility does not lie within the confines of the program but rather the leadership of the clinical institution to identify and promote potential candidates.
We are in a very exciting era of vision and ophthalmic research. Several ‘untreatable’ conditions are now actually or potentially treatable and the biopharmaceutical industry has appreciated just how important ophthalmology is. There are now several areas where ophthalmology is leading new developments that will then be adopted in other organ systems. Gene and cellular therapy programmes provide obvious examples. Ocular imaging is also becoming a powerful tool that has the potential to benefit management of systemic as well as ocular disorders. Despite this success, in terms of healthcare spend vision research remains relatively underfunded. We need to do more to increase the visibility of what we do.
Although vision research contributes to make our lives better, given, that roughly every second person in Europe has to cope with problems inflicting vision at some point in his or her life, our field lacks the proper awareness of the public, sufficient funding and support. As such, we need to increase awareness, that vision research needs more funding that yields sustainable research infrastructure in an aging society, where visual impairment may shadow the last decade of life. Although very well established in basic research, it is my belief that Europeans need to invest more in translational research including a clinical perspective. In difference to the US, where private donations are contributing at large, we need to motivate private philanthropists as well as the public towards donating funds for eye research.
What would you predict as the major challenges in Vision Research and Ophthalmology in the coming ten years?
In the field of inherited retinal degenerations definitely molecular diagnosis and therapies are the major challenges, hopefully to be overcome soon.
From a research perspective, a list of the most imminent diseases could be established in a rather short period of time. So, the challenge is not identifying which diseases should be addressed but rather how should the research for the identifying diseases be supported to an extent that allows quick advancement.
Therefore, the major challenge in vision research and ophthalmology is the increase in competition for funding within the field as well as with other disciplines. Two possibilities to overcome this significant obstacle are the following:
Inevitably funding is a major concern. There are so many opportunities to make major advances in vision research and ophthalmology at the moment that attracting an appropriate fraction of the life and medical sciences research budget at a time when total research budgets are being cut will be difficult. There is also a challenge to integrate eye disease into mainstream developments in systemic disorders and neurodegeneration, which I believe will be important both to understand fully the pathogenesis of many conditions but also to develop new models of healthcare that will serve the aging population.
The list of scientific challenges is very long! I am sure that the next 10 years will see huge advances in the understanding of how we see and the exploitation of that knowledge in the next generation of machine vision initiatives. We need to understand much more about the interplay of the vasculature, immune mechanisms and cell death in age-related macular degeneration and diabetic retinopathy
What would be you advice for Young Researchers and Clinicians in the field to advance their career prospects?
My suggestion to any young and ambitious researcher (whether working at the clinical or pre-clinical/basic science levels) is to get proper training in exceptionally productive and stimulating scientific environments. If this is abroad then even better. Proper training will give you those bases that will stay with you for the rest of your life and will be the key to advance in your career. So don't be shy about your future, go the best places and work very hard!
As they are young and well-qualified ophthalmologists I encourage them to travel and to practice in different European countries, to move towards hospitals and research centres providing surgical facilities as well as facilitating housing and support for young ophthalmologists.
Fortunately, the mentality within clinical medicine in Europe has changed since I was a medical resident. The barrier between academic and private institutions is weakening in the sense that more private institutions are engaging in research activities. For advice, I believe that if someone is interested in research, he/she should pursue it despite the traditional clinical track.
Personally, I switched from basic retinal to clinical corneal research after ten years and then later performed research in a private setting. Both of these decisions were unconventional, but the only thing that matters now was the quality of the research. And, I believe that I would not be at the position I am today if I did not take these chances with my career.
The most important thing is to pursue something that holds fascination and that you can be passionate about. Where possible (and this is not essential) there is much to be said for working in a high quality labs in stimulating environments. I believe that the greatest ‘risk factor’ for winning a Nobel Prize is to work in the lab of a Nobel laureate! It is critical to read and think widely. Great advances often flow from bringing together diverse ideas. Also consider taking an eye problem to a relevant outstanding lab with no experience in eye disease. It is critical to pay attention to developing creativity as well as an ability to execute experiments with the best possible scientific rigor. Creativity extends to asking the right questions as well as finding novel ways of seeking the answers. I do worry that the current environment can get too earnest and intense. Not good ingredients for creativity so work on ways of enhancing these skills too.