Understanding the Basis of Electrical Activity in the Central Retina to Improve the Diagnosis and Treatment of Retinal Degeneration

Michael Do, PhD
Children's Hospital Boston, Harvard Medical School (Boston, MA)
Year Awarded:
Grant Duration:
July 1, 2014 to June 30, 2016
Macular Degeneration
Award Amount:
Grant Reference ID:
Award Type:
Award Region:
US Northeastern

Mechanisms of Signaling in the Fovea


Few organisms have a more detailed visual experience than humans. The reason for that is humans possess a specialized part of their retina, called the fovea, that constitutes an extraordinarily “high definition” pixel array. Macular degeneration is a leading cause of blindness that devastates vision by attacking the fovea. By investigating how the fovea works, we will help further the diagnosis, prevention, and treatment of macular degeneration, while also gaining insight into how our power of sight outstrips that of most other creatures.


The goal of our project is to understand the process by which most visual experience is initiated in humans and other primates, thereby improving methods of diagnosing macular degeneration and related forms of blindness.

Our first aim concerns a population of highly specialized cells in the retina that originate high-acuity sight: the foveal cones. Like the pixels in a video camera, these cells convert light into electrical signals. These signals are processed by circuits in the retina and brain to generate our detailed and dynamic sense of the visual world. The foveal cones are so tiny, fragile, and rare that they have scarcely been studied before. We propose to decipher the inner workings of these enigmatic and important cells.

Our second aim is to lay the foundation for measuring the electrical activity of foveal cones using a method that is commonly available in the clinic, the electroretinogram. Foveal cones reside at the point where macular degeneration begins, and their death is what causes the loss of sight in this disease. We propose that the activity of foveal cones provides an early-warning system for macular degeneration. The challenge is to discern the electrical signature, or characteristic signaling, of foveal cones against the background of ongoing, unrelated activity in the remainder of the retina. We seek to define this electrical signature and develop a means of selectively analyzing it.

These experiments constitute the very first direct and systematic investigation of how foveal cones respond to light, and how their responses can be used to diagnose retinal health. Such investigation is unprecedented. The reason for that is that foveal tissue is scarce; it is also too delicate to study using standard research techniques. We have overcome these logistical and technical challenges. Thus, we are uniquely poised to undertake a series of groundbreaking experiments.

There are two immediate benefits to our research. First, we will gain new understanding of how sight is initiated by the fovea, a specialization of the retina that is found only in primates and endows them with a rarefied view of the world, one that is several-fold more detailed than that of any other mammal. Such understanding provides a platform for efforts to rebuild or replicate human sight. Second, we will use our knowledge of foveal cones to suggest ways of diagnosing macular degeneration earlier and more precisely, which will help in efforts to slow or even forestall this leading cause of blindness.

About the Researcher

Michael Tri H. Do is an assistant professor of neurology in the F.M. Kirby Neurobiology Center of Boston Children's Hospital and Harvard Medical School. His formal scientific investigations began in college, where he worked with Susette Mueller, PhD (Georgetown University) to study the mechanisms used by cancer cells to invade tissue. Dr. Do’s doctoral research was conducted with Bruce Bean, PhD (Harvard Medical School) and concerned the generation of spontaneous, electrical rhythms in neurons of the mammalian brain. Michael started investigating the visual system as a postdoctoral fellow with King-Wai Yau, PhD (Johns Hopkins University School of Medicine).