The major goal of our research is to understand the molecular and cellular basis of the functional development and regeneration of the vertebrate visual system and elucidate how disruption of the developmental mechanisms leads to visual dysfunction.
Vision is an essential experience for maintaining the quality of our daily life as its impairment severely compromises social interaction and independence. Our vision starts at the retina, the thin neural tissue at the inner surface of the back of the eye that captures visual scenes and sends the visual information to the brain. The retina is not a homogeneous array of neurons, but rather they contain areas of specialization that detect different visual information and therefore serve distinct visual requirements. This is exemplified in the small central part of the retina called the fovea. In humans and other primates, visual perception – with its appearance of rich and detail across most of the visual field – is predominantly driven by the information originating from a tiny high-acuity region of the fovea. However, despite the importance of this small part of the retina to our vision, the fovea and its surrounding area, the macular, are particularly prone to degenerative diseases such as age-related macular degeneration. In fact, macular degeneration is the leading cause of visual impairment in the US. However, it is still unclear why degeneration disproportionally affects the fovea. Our research focuses on
- Uncover developmental mechanisms for building the fovea. This is a key first step for understanding how the fovea is different from the periphery and why the fovea is more susceptible to degenerative diseases.
- Identify biological processes that cause degeneration in the macula.
- Discover new model animals for studying eye diseases.
We use zebrafish to study the development and degeneration of a macula. In our recent research, we discovered that the larval zebrafish retina contains a high-acuity region that resembles key aspects of the human fovea/macula. Zebrafish pose great advantages for studying the development of the eye because their development is very fast (forms fully functional retinal circuits within 5 days from birth) and transparent larvae allow us to monitor the developmental processes in living animals. Furthermore, we can readily manipulate their genetic components to highlight neurons of interest by expressing fluorescent proteins. We employ a wide range of techniques from various molecular methods such as single-cell RNA-sequencing, in vivo time-lapse imaging at synaptic resolution, electron microscopy neural circuit reconstructions, two-photon functional Ca2+ imaging, computational circuit modeling, and behavioral analysis.
In addition to zebrafish, we are actively looking for new model animals that feature human-like macula specializations. We have research projects at the bioRTC in Yobe State, Nigeria. One of the unique advantages of Africa is its rich biodiversity and abundance of wild animals. We are currently focusing on a lizard species, Agama, that is abundant in Yobe State. This lizard has a highly developed fovea at the center of the retina. Using this species, we are aiming to discover how the macula is formed during development and what makes the macula vulnerable to neurodegeneration diseases.