Chuanyu Guo
Diabetic retinopathy (DR) is the leading cause of vision loss among working-age people in the developed world. Currently, optimizing glucose management is the cornerstone for preventing diabetic eye disease. However, tight control of serum glucose concentration (TGC) has been associated with an early, paradoxical worsening of DR. Until recently, why TGC promotes an early worsening of DR has not been fully understood. One of the challenges of TGC is preventing hyperglycemic episodes without promoting increased episodes of hypoglycemia. We therefore proposed examining how the neurosensory retina responds to acute episodes of hypoglycemia, and how these responses may contribute to the development and/or progression of diabetic eye disease. In several cell-based, ex vivo and animal models, we observed that transient episodes of hypoglycemia resulted in HIF-1α accumulation and HIF- 1-dependent expression of angiogenic genes. In mice diabetic for as early as three months, prior to overt microvascular injury, hypoglycemia accelerated a synergistic increase in the accumulation of HIF-1α and the expression of HIF-regulated angiogenic factors. This, in turn, was sufficient in diabetic mice — but not control mice — to promote breakdown of the inner blood- retinal barrier (iBRB) and increased vascular permeability. Collectively, these observations help explain why patients with diabetes-initiating TGC have worsening of their DR. While TGC remains essential for preventing microvascular injury in patients with diabetes, our findings suggest that this should not be achieved at the expense of transient episodes of hypoglycemia. My whole work was conducted in Dr. Sodhi’s lab.
Questions & Answers
Why did you choose Johns Hopkins for your work?
Before I joined Johns Hopkins, I worked in retinal development research for several years, and I would like to transfer to studying mammalian models of human retinal disease. The Wilmer Eye Institute, Johns Hopkins Medicine
is excellent in both basic and clinical research on human eye disease. After talking with Dr. Sodhi, I was impressed by his intelligence, and I was sure that I would get a great opportunity for my postdoc training here.
What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received?
Receiving the Claude and Barbara Migeon Award is a great honor to me. This award is a recognition for my research and will motivate me to pursue my career goal in retinal diseases research. This award was established to honor the contributions of Claude Migeon and Barbara Migeon as both scientists and mentors. Their dedication to science will inspire me to move forward on the road of scientific research.
What contributed to your project’s success?
First, I’m grateful to my mentor, Dr. Sodhi, for giving me the opportunity to be trained in his lab. In his lab, he inspired me to propose a hypothesis and supported me to explore the hypothesis. Second, the training I received
in previous labs prepared me with technical skills to conduct experiments smoothly. Third, our collaborators helped us to confirm our results in different models.
What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Johns Hopkins?
Young Investigators’ Day provides a great opportunity for young investigators to share their research results and exchange ideas. This is also a chance to recognize the contributions of young investigators.
What has been your best/most memorable experience while at Johns Hopkins?
My most memorable experience at Johns Hopkins was that I got inspiration and inspired others when I discussed projects with my mentor and colleagues.
What are your plans for the next year or so? Graduating, looking for faculty positions, etc.?
Applying for NIH grants and looking for a faculty position.
Tell me something interesting about yourself that makes you unique. Do you have any special hobbies, interests or life experiences?
I like running. I finished two full marathons; one was in Baltimore last year. Running relaxes me and clears my mind. Many of my inspirations come when I am running.