This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Recent evidence outside of the eye indicates that the membrane domain protein, caveolin-1 (Cav-1) modulates inflammatory responses and innate immunity through regulation of Toll-like receptor (TLR) signaling. In autoimmune uveitis and diabetic retinopathy, conditions that share robust retinal inflammation as a pathological component, Cav-1 expression is dramatically upregulated in the retina. However, the role that Cav-1 plays in retinal inflammation has not been studied. We have used our COBRE support for this funding period to test the hypothesis that Cav-1 regulates inflammatory signaling in the retina. Microarray analysis of retinas/eyecups from Cav-1 null mice revealed that, of mRNAs with expression levels 2-fold or higher than controls, a large number are associated with immune responses or inflammatory signaling. The results reflect a shift toward a more pro-inflammatory retinal environment when Cav-1 expression is lost. Furthemore, we discovered a significant increase in the number of bone marrow-derived cells in the retinas of Cav-1 null mice by flow cytometry. Finally, we have found that Cav-1 null retinas display enhanced sensitivity to lipopolysaccharide, a TLR4 ligand. Our results suggest that Cav-1 may play an important role in the maintenance of the retinal immunosuppressive environment. We are now testing the hypothesis that retina-intrinsic expression of Cav-1 mediates this response using our recently generated retina-specific conditional knockout mice. Additional future experiments will determine whether the shift toward pro-inflammatory retinal environment is mediated by TLR signaling.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017703-10
Application #
8360406
Study Section
Special Emphasis Panel (ZRR1-RI-5 (01))
Project Start
2011-07-01
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
10
Fiscal Year
2011
Total Cost
$55,328
Indirect Cost
Name
University of Oklahoma Health Sciences Center
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
878648294
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117
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