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Monitoring microglial inflammatory phenotype in diabetic retinopathy models
Summary Data Summary
Applicant Abcouwer, Steven
E-Mail Address sabcouwe@med.umich.edu
Project Title Monitoring microglial inflammatory phenotype in diabetic retinopathy models
CBU ID 09MCG78
External SubContract ID
Diabetic Complication Retinopathy
Funding Program Group Pilot & Feasibility [PF2009]
Abstract We hypothesize that flow cytometry can be used to efficiently monitor the
activation and inflammatory status of retinal microglia during diabetic
retinopathy (DR). The Specific Aim is to demonstrate the feasibility of methods
to measure the activation and inflammatory status of retinal microglia during
the progression of DR. Microglia are resident macrophage cells in the central
and peripheral nervous system, and the sole immune cell of the retina. They
perform innate immune surveillance, becoming 鈥渁ctivated鈥 upon infection or
tissue damage. During acute and chronic neurodegenerative diseases microglia
become activated, exhibiting an altered phenotype that includes changes in
morphology, increased phagocytosis, surface marker expression, and gene
expression. Fully activated microglia produce inflammatory and toxic molecules
that contribute to neuronal inflammation, neuronal toxicity and vascular
dysfunction. Microglia exhibiting an activated morphology have been observed in
both human diabetic retinas and experimental models of DR. Immunohistochemical
co-staining for inflammatory proteins and microglial marker proteins have
qualitatively cemonstrated that activated microglia are a potential source of
inflammatory proteins during retinopathies. However, during some
neurodegenerative diseases microglia assume an alternative activation phenotype
that coincides with the expression of anti-inflammatory proteins. These
microglia may actually play a beneficial adaptive role that minimizes the
inflammatory response to neuronal damage. Given that inflammation is now thought
to play a key role in the progression of DR, it is vital to define the
activation and inflammatory status of retinal microglia. The goal is to perfect
methods enabling the expression of several inflammatory proteins, including
TNFa, IL-6, IL-1脽, and iNOS, as well as anti-inflammatory proteins, including
TGF脽, IL-1Ra, IL-27, and arginase, to be quantified in subsets of retinal
microglia by flow cytometry. To accomplish this we will: 1) use cultured
microglia to initially test and develop antibody combinations for use in flow
cytometry, 2) further test these combinations using the retinal IR model, and 3)
apply these methods to retinas of diabetic animals.
Application PDF Application Research Plan
Status Awarded
Key Personnel
Salary Total Costs 26574
Supply Total Costs 12172
Equipment Total Costs 0
Travel/Other Total Costs 15800
Direct Costs 54546
Indirect Costs Proposed 5454
Total Costs Proposed 60000
Total Costs Approved 63000
Start Date
End Date
IFO Name Falvo, Vincent
IFO E-Mail Address vfalvo@hmc.psu.edu
IACUC/IRB No. pending
IACUC/IRB Institution Pennsylvania State University-Penn State College of Medicine
Entity ID No. 1246000376A3
Report Request Date
T1D NO
TypeCount
Invoices 0
Progress Reports 0
Data Submission
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