Tuesday, May 13, 2025
5/13/2025
Development of Retinal Ganglion Cell types - Project Summary The retina transforms the visual scene into ~30 different channels of information, each mediated by a unique type of retinal ganglion cell (RGC). RGC types differ in their morphology, functional response properties, brain targets, and the behaviors in which they participate. For reasons that are not yet known, different RGC types have different susceptibilities to cell death after optic nerve injury. Several fundamental aspects of each RGC type remain unknown: how each develops and maintains its unique characteristics, how each contributes to the visual response properties of neurons in the brain, and contributes to visually induced behaviors. Filling this gap in knowledge is not only a prerequisite to understand how the visual system functions, it is also necessary if we are to either salvage or regenerate RGCs that can integrate into the retinal circuitry and maintain their function after injury or disease. Satb1 and Satb2 are expressed in mouse DS RGCs and removing Satb1 and Satb2 during development leads to the loss of direction selective retinal responses. Experiments in Aim 1 are designed to elucidate the role of Satb1 and Satb2 in RGC development and to test the hypothesis that On-Off DS RGCs contribute to the formation of direction selective cells in the brain and to motion visual behavior. In Aim 2 we will test the hypothesis that Tbr2 is necessary and sufficient for the development and maintenance of non-image forming RGCs. Tbr2 is expressed in newly differentiated RGCs and expression continues into adulthood. Mice lacking retinal Tbr2 during development fail to form non- image forming circuits and lose light-dependent reflexes. We will test the hypothesis that Tbr2 is required for maintaining a non-image forming RGC fate and by over expressing Tbr2 we will determine if Tbr2 is sufficient to change developing or adult RGCs to a non-image forming fate. In Aim 3 we will examine if Tbr2 is necessary and sufficient for neuroprotection of RGCs after injury. The optic nerve crush assay is used as a model to study the mechanisms counter to degeneration, namely RGC survival and regeneration. We find that Tbr2 expressing RGCs are selectively spared after nerve crush. Experiments in this aim will determine the role of Tbr2 in RGC survival. Upon completion of these aims we will significantly advance our understanding of how direction selectivity is generated during development, discover mechanisms used to maintain RGC health and function after its incorporation into circuits, and discover new mechanisms of neuroprotection.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).