Development of functional plasticity in a simplex retina. - PROJECT SUMMARY/ABSTRACT: Retinal sensitivity over the full range of environmental lighting conditions, from dark to bright, is mediated by rod and cone photoreceptors and is fundamental to vision. Importantly, when one type of photoreceptor dies, as in retinal diseases like macular degeneration or retinal dystrophy, the remaining photoreceptor type is unable to fill-in the gap in functionality that remains. This often leads to visual impairment or blindness. Disorders of the visual system that selectively damage photoreceptors affect millions of people worldwide. In the United States alone, age-related macular degeneration is the leading cause of blindness for people over 65 – an affected population that is projected to double in the next 25 years. Other rarer conditions, like retinitis pigmentosa and retinal dystrophies, affect ~1 in 4000 or 5000 people, respectively. Predictably, rescuing lost function in photoreceptors is a major goal in vision restoration efforts. However, the majority of mammalian retinas are “duplex” and have mixed rod-cone populations. Duplex retinas experience a “duality barrier” to restoring function after the selective loss of one type of photoreceptor. Retinas of other vertebrate organisms present us with exciting new opportunities to understand how we could possibly overcome the “duality barrier”. Here, we propose to investigate the pure-rod retina of Leucoraja erinacea (Little Skate), in which a single class of photoreceptor can subserve the full range of rod and cone vision. We have a limited understanding of what environmental and developmental factors govern this functional plasticity in the skate retina, but a detailed knowledge of how this is achieved could hold the key to expanding the functional repertoire of surviving rods or cones in diseased duplex retinas. Based on previous work and preliminary data, we hypothesize that this functional plasticity is driven by developmental programs under the influence of early sensory input, leading to the adaptations observed in the mature retinal circuit. We will test our hypothesis in the following specific aims: Aim 1: To determine what molecular and structural factors govern the establishment of cell circuitry in a functionally plastic single photoreceptor type retina during development. The objective of Aim 1 is to understand how early and late developmental stages shape the establishment of functional plasticity. Aim 2: To determine the role of sensory experience and light adaptation in the formation and function of rod circuitry on the anatomical, physiology, and molecular level. The objective of Aim 2 is to understand the effects of sensory deprivation on the development of a functionally plastic retinal circuit. The proposed research is innovative because it steps away from a traditional mixed rod-cone retina model system and instead studies the functional adaptation of rod circuitry in a naturally occurring pure-rod retina model system. It is significant because it will reveal fundamental principles of functional adaptation in a single photoreceptor type retina, which can lead to novel vision restoration efforts focused on expanding the functionality of surviving photoreceptors.
