Developmental and age-related disorders that affect vision impart a major social and economic burden on the US economy. Many of these disorders specifically affect neurons that connect the retina (i.e., retinal ganglion cells [RGCs]) information to the brain. The most common of these disorders is glaucoma, a progressive neurodegenerative eye disorder that is the leading cause of irreversible blindness in the US. Currently, 3 million Americans are living with glaucoma, costing the US economy nearly 3 billion dollars each year. Glaucoma is not the only disorder that impacts RGCs. Currently there are no effective treatments for patients with glaucoma. In response to this unmet need, NEI has issued a goal of gaining new knowledge that will contribute to the development of regenerative therapies aimed at restoring connections between the retina and brain. To accomplish this goal, we need a better understanding of the mechanisms that drive the formation of these connections during normal development. Over the past 5 years, we investigated the mechanisms that drive the growth of retinal axons into appropriate target regions of brain. During this work, we discovered that retinal synapses in the dorsal lateral geniculate nucleus (dLGN) are anatomically and functionally distinct from retinal synapses in all other retino-recipient regions. Because these synapses are crucial for transmitting visual information to cortex, understanding mechanisms of their formation is essential for restoring subcortical visual circuit function. With this in mind, the objective of this application aims to identify target-derived cues responsible for the unique development of retinogeniculate synapses in dLGN. Preliminary experiments identified Insulin-like Growth Factor 1 (IGF1) and Leucine-Rich Repeat Transmembrane Neuronal Protein 1 (LRRTM1) as two synaptogenic cues expressed in dLGN. Here will will use molecular, genetic, anatomical and physiological approaches to assess roles of these molecules in retinogeniculate circuit formation.
Visual impairment imparts major social and economic burdens on the US population. Currently, there are no effective therapies to regenerate visual circuits and restore vision in affected persons. In response to this unmet need, this project aims to reveal important information about retinal and subcortical visual circuit development, thereby fostering the design of new treatments for visual impairment.
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| Monavarfeshani, Aboozar; Stanton, Gail; Van Name, Jonathan et al. (2018) LRRTM1 underlies synaptic convergence in visual thalamus. Elife 7: |
| Araújo, Sheila Espírito Santo; Mendonça, Henrique Rocha; Wheeler, Natalie A et al. (2017) Inflammatory demyelination alters subcortical visual circuits. J Neuroinflammation 14:162 |
| Monavarfeshani, Aboozar; Sabbagh, Ubadah; Fox, Michael A (2017) Not a one-trick pony: Diverse connectivity and functions of the rodent lateral geniculate complex. Vis Neurosci 34:E012 |
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| El-Danaf, Rana N; Krahe, Thomas E; Dilger, Emily K et al. (2015) Developmental remodeling of relay cells in the dorsal lateral geniculate nucleus in the absence of retinal input. Neural Dev 10:19 |
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