Establishing the Foveal Retina During Embryonic Development

The central retina is the small portion of the eye used for our clearest and sharpest vision. Anatomically, it is different from the rest of the eye, and we do not understand exactly why. The central retina is specifically affected by several eye diseases, and discovering what makes it unique can help with treatment and future therapies for re-growing this portion of the eye. As our research proposal, we will utilize a bird model to first follow the development of the precursors to the central retina cells. Next, to determine which, if any, of the environments that they pass through during development are important for making them specific to the central retina tissue.

Having found evidence that the process of embryonic retinal development may be distinct for cells that provide peripheral versus central vision, our research goal is to identify the definitive origin and specific developmental mechanisms underlying the establishment of central neural retina (cNR) cells, specifically, in an avian model.

Eye formation proceeds over several days of embryonic development, and it is not known when or how the cNR is determined. In our first set of experiments. we are mapping the locations of the cells in early embryos that will contribute to the cNR. Using specialized tools, we label small groups of cells and follow them, thereby directly visualizing their eventual contribution to the eye. Once we can identify the location of the cells that will populate specifically the central or peripheral retina, we will look at the environment around the future cNR to identify the neighboring tissues that may instruct the developing retina. Using microsurgery to delete and replace identified target tissues, we will uncover the specific tissue interactions that determine a cNR fate in the emerging eye.

Our work, for the first time, identifies heterogeneity in retinal origin. Building on this, our studies challenge our fundamental understanding of retinal development. It is well understood that the central retina is a specialized region of high visual acuity, but to date, there has not been a method to easily study the development of the sub-structure, because the eye develops over such a prolonged period. We will use a classic avian model system and apply novel tools and enhanced optics, enabling us to manipulate the embryo at very early stages and follow the entire period of eye development. Further investigation may provide an understanding of why the macula (at the center of the retina) is more likely to degenerate than other retinal cells in patients with macular degeneration.