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The Ins2Akita mouse as a model of vision loss and neurodegeneration in diabetes
Summary Data Summary
Applicant Barber, Alistair
E-Mail Address abarber@psu.edu
Project Title The Ins2Akita mouse as a model of vision loss and neurodegeneration in diabetes
CBU ID 09MCG66
External SubContract ID 20497-31
Diabetic Complication Retinopathy
Funding Program Group Pilot & Feasibility [PF2009]
Abstract The overall goal of this research is to determine the mechanism of vision loss
in diabetic retinopathy. The main objective of the proposed project is to
develop functional assays of vision loss in the spontaneously diabetic Ins2Akita
mouse, and compare the loss of function with assays of cell death, retinal
morphomotry (cell layer thickness and nuclear counts) and synaptic protein
content. A new approach that uses the optokinetic reflex will be employed to
measure visual acuity and contrast sensitivity in mice. We have also established
that a rapid and sensitive cell death ELISA can be used to measure apoptosis in
mouse retinas. This assay measures the amount of nucleosomal fragments in the
cytoplasm of cells undergoing apoptosis. Furthermore, our published data show
that the content of a group of pre-synaptic proteins is depleted in the retinas
of diabetic rodents, and that diabetes leads to reductionsin the thicknes of the
inner retinal layers in mice and rats. These assays can be used to measure loss
of function, apoptosis, retinal degeneration and synaptic malfunction in
Ins2Akita diabetic mice. Therefore this project will test the general hypothesis
that diabetes induces retinal neurodegeneration and compromises visual function
in the Ins2Akita mouse. The first specific aim is to measure vision loss,
apoptosis and retinal morphomotry in diabetic Ins2Akita mice after different
durations of diabetes. The second specific aim is to measure vision loss and
synaptic protein content in Ins2Akita mice, again after different durations of
diabetes. It is predicted that apoptosis will be detected soon after the onset
of diabetes and that visual acuity and contrast sensitivity will be correlated
with loss of the retinal cell layers and with reduced synaptic protein content.
This project will further establish the Ins2Akita mouse as a model of diabetic
retinopathy, and will test the concept that retinal cell apoptosis and synaptic
degeneration lead to vision loss. Furthermore, it will identify the threshold of
synaptic protein and retinal cell loss that is required to cause a measurable
loss of function in the Ins2Akita mouse.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 34555
Supply Total Costs 18990
Equipment Total Costs 0
Travel/Other Total Costs 1000
Direct Costs 54545
Indirect Costs Proposed 5455
Total Costs Proposed 60000
Total Costs Approved 63000
Start Date 9/1/2009
End Date 8/31/2010
IFO Name Yarnell, Michael
IFO E-Mail Address e-grants@hmc.psu.edu
IACUC/IRB No. ATMCG
IACUC/IRB Institution Pennsylvania State University-Penn State College of Medicine
Entity ID No. 129348186
Report Request Date 9/30/2010
T1D NO
TypeCount
Invoices 0
Progress Reports 1
Experiments 1
Data Submission


Experiments
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