【Michiko Mandai (Regenerative Medicine)】If It Isn't a Good Treatment, It Won't Last: Taking on the Challenge of Regenerative Medicine Ahead of the World
＜Profile＞
Michiko Mandai, MD, PhD
Director, Research Center, Kobe City Eye Hospital
Dr. Michiko Mandai graduated from Kyoto University Faculty of Medicine in 1988 and earned her PhD from the same institution's Graduate School of Medicine in 1994. She engaged in clinical practice and research at Kyoto University Hospital and the National Institutes of Health (NIH) in the United States. In 2006, she joined the RIKEN Center for Developmental Biology to participate in retinal regenerative medicine research, leading landmark clinical research using iPS cells as RIKEN Deputy Project Leader and Photoreceptor Research Team Leader. In April 2022, she was appointed Director of the Research Center at Kobe City Eye Hospital, where she continues to lead at the forefront of retinal regenerative medicine.
Areas of Expertise: Regenerative Medicine, Macular Diseases
【Background】Cherishing Childhood Memories: Rich Nature and a Lively School Life
Could you share a bit about your background?
I was born in Okayama Prefecture. During my early childhood, we moved to Hiroshima, followed by a brief period in Mukonoso (Amagasaki City, Hyogo Prefecture), before settling in Nagaokakyo City, Kyoto Prefecture, from my kindergarten years onward. Back then, Nagaokakyo was a tranquil, beautiful place surrounded by rice paddies, and I vividly remember watching swarms of fireflies dancing in the summer air. Later, because I attended Kobe College for middle and high school and my father worked in Osaka, our family moved back to Mukonoso when I was in high school.
What memories stand out from your school years?
My time at Kobe College was truly wonderful. Every morning, the entire school would gather for chapel service and sing two hymns at the beginning and two at the end. I loved singing, so participating in the morning service—choosing my preferred vocal part, singing in harmony with everyone, and hearing students add descants—was a pure joy. In fact, one of the things I missed most after graduating was no longer singing hymns every morning. Since the school was founded by American female missionaries, the Christmas service—which turned into a full-choral performance—was absolute bliss. We also put on "stunts" (short comedy skits) for various school events. Looking back, those shared moments are among my fondest memories.
【Career Choice】From Psychology and Psychiatry to the Bright and Open World of Ophthalmology
What led you to choose a career in ophthalmology?
At the time, Freud’s psychoanalysis and Jung’s analytical psychology were widely popular, and I was fascinated by them. Professor Hayao Kawai, who introduced Jungian psychology to Japan, was teaching at Kyoto University, which made me think, "I want to study at Kyoto University." Professor Kawai wasn't in the Faculty of Medicine, though!
Building on that interest, I thought that if I were to go into medicine with future employment in mind, I would choose psychiatry. However, once I entered medical school, I realized my expectations didn't quite match reality—at the time, psychiatry still retained strong remnants of the student movement, and Kyoto University's medical school wasn't necessarily the right environment if my primary goal was studying pure psychoanalysis.
Up until high school, I had a somewhat introverted personality, naturally drawn to psychology and the inner workings of the mind. But university life turned out to be so fulfilling that I became thoroughly balanced and outward-looking. Rather than focusing on the "inner mental world," I felt a growing desire to contribute to society in a more practical way, which drew me toward surgical disciplines.
Among the various departments, ophthalmology stood out. It had a relatively high proportion of female physicians, surgeries were largely performed on an individual basis, and there was already an early appreciation for work-life balance and a very bright, open atmosphere. The department also actively encouraged studying abroad—something I had long dreamed of doing. All these factors made choosing ophthalmology a natural decision.
【Specialty】Navigating Clinical Practice and Basic Research Toward Regenerative Medicine
Could you walk us through your career after choosing ophthalmology?
As I treated patients, I became increasingly curious about what was happening inside the eye and why certain conditions developed. I realized I wanted to explore these questions through experiments to find definitive answers. When asking myself, "What treatment can truly cure this disease?", observing clinical outcomes alone rarely provides clear answers, nor does it allow for proactive intervention. I felt that conducting various experiments would be the key to uncovering those answers, which sparked my interest in research. After spending two years in clinical practice, I entered graduate school to pursue research, and after completing my degree, I continued balancing both clinical care and research.
A little over a decade into my medical career, I had the opportunity to study at the National Institutes of Health (NIH) in the United States for two years. Stepping away from clinical ophthalmology, I focused entirely on basic research at the NIH. During that time, Dr. Masayo Takahashi (President of Vision Care Inc. and Advisor to the Research Center at Kobe City Eye Hospital) was appointed associate professor at Kyoto University Hospital's Translational Research Center—a facility established to bridge basic research findings with clinical applications. Dr. Takahashi invited me to join her team, so upon returning to Japan in 2002, I joined the center.
At the Translational Research Center, I was initially responsible for setting up genetic diagnostics for retinitis pigmentosa. Around 2006, we moved to RIKEN, where I gradually began engaging in regenerative medicine research—the core focus of our laboratory. Alongside my research, I maintained a weekly clinical presence, diagnosing patients with age-related macular degeneration at the Macula Clinic of Kobe City Medical Center General Hospital.
What led you to specialize in macular diseases within your clinical practice?
To be honest, I was initially assigned to the macula clinic almost by chance, so I don't remember the exact details. However, examining the macula—the central area directly responsible for vision—proved to be fascinating, which is why I chose to stay with it. While effective treatments exist today, when I first started at the macula clinic, options for age-related macular degeneration were virtually limited to laser photocoagulation for a very small subset of patients. Because the macula is the center of vision, even the slightest change immediately affects how a person sees, making it a truly compelling field to study.
【Reflections】"You Changed My Life": The True Joy of Restoring Vision
Could you share a memorable experience with a patient?
I truly believe that sight is one of the most vital aspects of human life. Far beyond what we as ophthalmologists might imagine, even a subtle improvement in vision can lead patients to tell us, "You changed my life."
I recall treating a photographer some years ago. He was suspected of having macular degeneration, and at the time, laser therapy was practically the only treatment option available. However, if applied incorrectly, laser treatment carried the risk of triggering neovascularization and worsening the condition, so I hesitated to perform the procedure.
I explained to him, "There are risks involved, so let's observe your condition for a while." But the patient urged me strongly, saying, "Even if something goes wrong, I won't hold it against you. Please treat me." Despite my anxiety over what felt like a fifty-fifty chance of success, I proceeded with the laser treatment.
When he returned for his next visit, he had a beaming smile and said, "The autumn leaves on the mountains are so breathtakingly beautiful." I remember that moment vividly. Relief washed over me, but it also taught me a profound—if delicate—lesson: sometimes, placing trust in a patient's courage is an essential part of advancing treatment. Whenever a patient tells me that regaining their sight has transformed their life, it brings me genuine joy.
【Ophthalmology in Japan】Surgical Skill, Cutting-Edge Technology, and Attentive Patient Care
What do you see as the strengths of ophthalmology in Japan?
Ease of access to medical care is undoubtedly one of Japan’s greatest strengths. Overseas, it is quite common to wait months just to be examined for a minor condition, whereas in Japan, that is rarely the case.
Additionally, Japanese surgeons are exceptionally precise and skillful on average, and there is a strong culture of diligence. While outstanding surgeons certainly exist all over the world, I feel that the overall baseline of surgical competence in Japan is remarkably high.
Thorough diagnostic testing is another compelling advantage Japan offers compared to other countries. I think Japanese physicians, in general, have a strong affinity for technology—they love acquiring images and analyzing them. It is often said that, even beyond ophthalmology, no country utilizes CT scans as extensively as Japan. Whenever new diagnostic equipment is introduced, many doctors here eagerly and enthusiastically dedicate themselves to image-based research.
I also frequently hear from international patients who are moved by the polite, attentive care rooted in Japanese hospitality. While every system has its pros and cons, medical systems abroad often emphasize strict professional boundaries and specialization. Consequently, healthcare staff rarely step outside their designated roles. In Japan, however, physicians and staff often rely on their own initiative to cover various tasks, even when thinking, "This might not strictly be my responsibility." I believe that kind of flexibility is also a key strength for Japan.
【Regenerative Medicine for the World】If It Isn't a Good Treatment, It Won't Last
What are your thoughts on delivering regenerative medicine to patients abroad?
Thanks to the extraordinary efforts of Dr. Masayo Takahashi, I believe the regenerative medicine initiatives we are currently pursuing remain ahead of the world.
Naturally, the best outcome for patients is for the therapy to become accessible locally. Even if patients initially need to travel to Japan for treatment, it would be ideal if we could coordinate follow-up care with trusted local physicians, thereby allowing regenerative medicine to spread globally through those physician networks.
However, beyond delivering treatments as quickly as possible, I strongly feel that "if it isn't a truly good treatment, it won't last." Strategic approaches are important, but as various products enter the market, anything that isn't genuinely effective will eventually be phased out. Securing funding for developing "ever-better therapies" has been challenging recently, but taking a long-term view, we must develop therapies of the highest possible quality—both to ensure they endure and to maintain sustained corporate backing.
How do you think Japanese ophthalmic researchers should engage with the global community?
When it comes to research, I believe the best stance is always "let's work together." We occasionally receive invitations for international collaborations. While matters like intellectual property licensing can be complex, building a network of trusted peers with whom we can share information—rather than viewing them merely as rivals—ultimately leads to more successful treatment development.
【About the Hospital】Comprehensive Care Beyond Treatment: The Strength of Kobe City Eye Hospital
What makes Kobe City Eye Hospital unique?
A key feature of our hospital is that we conduct advanced clinical research and clinical trials alongside routine medical care. Being more agile than a traditional university hospital allows us to stay closer to our patients, which I consider a great advantage.
Furthermore, our hospital brings together physicians who are passionate about both clinical practice and research—doctors who are not satisfied with simply delivering standardized treatments, but who actively dig deeper. It is a place driven by strong curiosity and a commitment to lifelong learning.
The presence of NEXT VISION, a public interest incorporated association located within the same facility, is also immensely significant. NEXT VISION provides low vision care—a form of holistic support spanning education, employment, social integration, welfare, and psychological care, beyond conventional medical treatment. While many eye conditions still cannot be cured, how patients utilize their remaining vision can dramatically change their quality of life. Being directly connected with NEXT VISION enables us to support patients even when medical treatment is no longer an option. As doctors, we often wish there were more we could do for patients we cannot cure, so being able to refer them to low vision care is something we are deeply grateful for.
Looking ahead, it would be wonderful to expand our international presence even further, while also collaborating with Vision Forth Inc. Thanks to our ties with RIKEN, our network with international researchers and physicians continues to grow. We already have overseas researchers visiting us simply because they want to experience Kobe Eye Center, as well as those coming for collaborative research. There are very few municipal hospitals quite like this, making it a truly fascinating institution.
Kobe City Eye Hospital
2-1-8 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, Japan
※Approximately 2 minutes walk from Medical Center Station (Port Liner)
Clinic Hours: 8:45 AM – 11:00 AM (Closed: Saturdays, Sundays, National Holidays, and Year-End/New Year Holidays [Dec 29 - Jan 3])
