UNIVERSITY OF WASHINGTON
This is a request for supplementary funds to support the appointment of an additional Research Scientist and obtain new instrumentation to expand the library of constructs for investigation of protein aggregation disease in vivo. While it is well known that the accumulation of unfolding proteins initiates the formation of amyloid/aggregates, previous research has been limited to cell culture, in vitro or in silico studies. The current active grant studies the initiation and growth of the aggregates in living animal using non-invasive methods. The additional Research Scientist and instrumentation will dramatically increase the tempo of scientific research on AIMS 2 and 3 of the current active grant, 5RO1 EY004542 (Dates of Activity: 04/01/2009 - 03/31/2014). AIM 2 of the current application conducts slit lamp examinations of both the transparent structure and aggregate/amyloid formation in lenses in novel transgenic mouse models for neurodegenerative and neuromuscular disorders. AIM 3 of the current application correlates the protein composition with the structure of transparent and opaque lens cells in wt and transgenic mouse models for neurodegenerative and neuromuscular disorders. It is well established that neurodegenerative diseases, Alzheimer's, Parkinson's and Huntington's, are protein unfolding and aggregation diseases. It is not widely recognized that neurodegenerative processes underlie the leading causes of blindness: macular degeneration, glaucoma, diabetic retinopathy, retinal degeneration and cataract. The novel constructs generated by hiring a Research Scientist using supplemental funds will be used in the development new animal models for testing protective agents against aggregation diseases in the brain and eye.