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.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1-RI-5 (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Oklahoma Health Sciences Center
Schools of Medicine
Oklahoma City
United States
Zip Code
Vieira, Frederico; Kung, Johannes W; Bhatti, Faizah (2017) Structure, genetics and function of the pulmonary associated surfactant proteins A and D: The extra-pulmonary role of these C type lectins. Ann Anat 211:184-201
Simón, María Victoria; Agnolazza, Daniela L; German, Olga Lorena et al. (2016) Synthesis of docosahexaenoic acid from eicosapentaenoic acid in retina neurons protects photoreceptors from oxidative stress. J Neurochem 136:931-46
Stiles, Megan; Qi, Hui; Sun, Eleanor et al. (2016) Sphingolipid profile alters in retinal dystrophic P23H-1 rats and systemic FTY720 can delay retinal degeneration. J Lipid Res 57:818-31
Bennett, Lea D; Anderson, Robert E (2016) Current Progress in Deciphering Importance of VLC-PUFA in the Retina. Adv Exp Med Biol 854:145-51
Ding, Xi-Qin; Thapa, Arjun; Ma, Hongwei et al. (2016) The B3 Subunit of the Cone Cyclic Nucleotide-gated Channel Regulates the Light Responses of Cones and Contributes to the Channel Structural Flexibility. J Biol Chem 291:8721-34
Ma, Hongwei; Ding, Xi-Qin (2016) Thyroid Hormone Signaling and Cone Photoreceptor Viability. Adv Exp Med Biol 854:613-8
Cai, Xue; Chen, Lijuan; McGinnis, James F (2015) Correlation of ER stress and retinal degeneration in tubby mice. Exp Eye Res 140:130-138
Bhatti, Faizah; Ball, Genevieve; Hobbs, Ronald et al. (2015) Pulmonary surfactant protein a is expressed in mouse retina by Müller cells and impacts neovascularization in oxygen-induced retinopathy. Invest Ophthalmol Vis Sci 56:232-42
Logan, Sreemathi; Anderson, Robert E (2014) Dominant Stargardt Macular Dystrophy (STGD3) and ELOVL4. Adv Exp Med Biol 801:447-53
Marchette, L D; Sherry, D M; Brush, R S et al. (2014) Very long chain polyunsaturated fatty acids and rod cell structure and function. Adv Exp Med Biol 801:637-45

Showing the most recent 10 out of 244 publications