Retinal neural processing during retinal degenerative diseases

Winifred Masterson Burke Med Res Inst, White Plains NY

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Abstract

ABSTRACT Retinal degenerative diseases, such as macular degeneration and retinitis pigmentosa, are among the leading causes of blindness. Current treatment strategies are aimed at restoring light sensitivity, and assume that surviving retinal circuitry remains relatively intact as photoreceptors degenerate. This paradigm is being challenged by recent findings that reveal a massive structural remodeling of the retina during and after photoreceptor death; retinal circuits compensate for the loss of photoreceptor input during a phased process of remodeling. Although such changes could preclude every aspect of retinal repair by forming networks incapable of transmitting visual signals, the synaptic basis for these changes is unknown. To fill in this gap, in Aim 1, we will record resting activity of identified retinal ganglion cells in mouse models of retinal degeneration to determine the synaptic mechanisms responsible for altered retinal output during progression of the disease. In Aim 2, we will drive retinal circuits with presynaptic stimuli to determine the ability of ganglion cells to process synaptically-evoked responses. Since ganglion cells are the output neurons of the retina, their synaptic inputs reflect the functional state of the retinal circuits responsible for visual processing. Identifying these changes could help to reduce the impact of retinal degeneration by providing new targets to repair or prevent retinal dysfunction.