The discovery of ocular lymphatics: Q&A with LMP alumnus Alex Tam
For over a century, scientists believed that the eye lacked lymphatics. However, research conducted by LMP alumnus Alex Tam (MSc) and Professors Yeni Yücel (MD, PhD, FRCPC) and Neeru Gupta (MD, PhD, MBA) has identified ocular lymphatics and demonstrated their role in fluid drainage from the eye. Their groundbreaking research, Latanoprost Stimulates Ocular Lymphatic Drainage: An In Vivo Nanotracer Study, was recently published in Translational Vision Science & Technology.
In this Q&A, Tam describes his research and how the evidence of lymphatics could revolutionize the treatment for reducing eye pressure and prevent blindness caused by glaucoma.
1. What has your research shown? The results demonstrated in the article were built upon the previous identification of lymphatic channels and their role in fluid drainage in the human and sheep eye. Using a newly developed non-invasive imaging technique, a lymphatic drainage pathway was shown from the mouse eye. In addition, this is the first evidence that latanoprost, the most commonly prescribed glaucoma eye drop, increases this newly identified lymphatic drainage from the mouse eye.
2. What did scientists previously believe? Scientists previously believed lymphatics did not exist in the eye, therefore not contributing to fluid drainage from the eye. Our lab was the first to identify lymphatic channels and to demonstrate their role in fluid drainage in the human and sheep eye. This latest work supports the existence of an ocular lymphatic drainage in mouse, which is a model used to study many diseases.
Scientists believe that the mechanism of action for latanoprost to increase fluid drainage is partly due to remodelling of the extracellular matrix composition. This paper provides evidence that latanoprost also stimulates ocular lymphatic drainage.
3. Why are you interested in this area of research? I first began my research project as a summer research student under Dr. Yeni Yucel and Dr. Neeru Gupta who are both clinician-scientists. They helped me understand that my project was more than discovering new knowledge of the eye - but may help lead to the development of medications to preserve the vision of patients with glaucoma. My personal experiences with eye injury allowed me to relate to the negative impact of vision loss on the quality of life. Hence, being able to make scientific discoveries while contributing to the prevention of blindness inspired me to continue the project as my Master's thesis.
4. What methods did you use for your research and why were they leading-edge? The core methods utilized involved two steps: 1) injection of nanocrystal tracers, quantum dots (QDs), into the mouse eye; and 2) visualizing the in vivo trajectory of QDs at various times using an in vivo hyperspectral fluorescence imaging system.
Conventional methods to visualize the lymphatic network in other tissue systems utilize radioactive tracers or organic fluorophores. However, these tracers require invasive methods. In contrast, the unique physical and optical characteristics of QDs make them suitable for non-invasive in vivo imaging. The size of QDs provide optimal uptake and retention inside lymphatic vessels and lymph nodes. QDs can be detected by hyperspectral imaging due to an intrinsic brightness greater than regular organic fluorophores. The emission spectrum of QDs can be distinguished from autofluorescence signal by the hyperspectral imaging system.
5. What are the implications? Glaucoma is a leading cause of irreversible blindness worldwide. It is estimated to affect 80 million people in 2020. Lowering eye pressure with medicated eye drops to improve fluid drainage from the eye helps to preserve vision in glaucoma patients. Surgical treatments with additional risk of vision loss may be needed if these do no control eye pressure. So there is a compelling need for new drug choices to care for patients with glaucoma. By demonstrating the existence of a lymphatic drainage from the mouse eye, and an increased ocular lymphatic drainage rate with application of latanoprost, this new work supports the use of a mouse model as an ideal platform for pharmacological manipulation of this newly identified outflow pathway. This may be highly relevant to treatments aimed at lowering eye pressure to prevent blindness from glaucoma.
Lymphatics are also known to play a role in immune responses and cancer metastasis. Hence, areas involving ocular inflammation or development and spread of intraocular tumors can be further explored in the future.
6. What are the next steps for this research? Existing glaucoma mouse models provide opportunities to study whether ocular lymphatics can be targeted to control eye pressure, thereby delaying onset or progression of glaucoma. With the newly developed method combining injection of QDs in to the eye and in vivo hyperspectral imaging, we aim to screen various compounds and determine which can stimulate the ocular lymphatic drainage and lower eye pressure in the glaucomatous mice. It may take several years to screen for new compounds suitable for clinical trials.
7. What are your next steps? I will begin my medical education at the Faculty of Medicine, the University of Toronto, in the fall of 2014. In the future, I will pursue additional training to become a clinician-scientist. I hope to improve people's quality of life through broadening our scientific and medical knowledge and applying it in clinical settings.
8. What advice do you have for potential graduate students? Graduate studies involve an immense amount of commitment and hard work, and the paths may be rough. Being able to contribute to science that is relevant to patient care, while simultaneously having fun with classmates and faculty members will make any pain and sweat well worth the rewards.