The project will study the response of the tight junctions (TJ) to experimental dry eye (EDE) on the corneal epithelium with specific emphasis on the perturbation of corneal epithelial barrier function. Corneal epithelial barrier will be evaluated as the uptake of Oregon Green Dextran, a high molecular weight fluorescent molecule (70kda) and it will be correlated to the expression of TJ proteins and late envelope proteins (LEP) prior to and after 1,3,5,7,10 and 12 days of EDE. This study will also evaluate the role of pro-inflammatory signaling mediators on expression of TJ and LEP in response to EDE. Effectiveness of specific inhibitors of stress associated pathways/mediators will be evaluated in the prevention of corneal barrier dysfunction. The dry eye will be induced in mice by pharmacologic inhibition of tear secretion with scopolamine and placement in an environmentally controlled chamber with low humidity and a constant air draft. Real time PCR will be used to evaluate the gene expression of pro inflammatory mediators. TJ and LEP expression will be evaluated by laser scanning confocal microscopy and immunostaining. Pro inflammatory mediator expression will be evaluated by Western Blot, ELISA and the Luminex Multiplex Assay. ? ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32EY016928-01
Application #
6999263
Study Section
Special Emphasis Panel (ZRG1-F01 (20))
Program Officer
Fisher, Richard S
Project Start
2005-09-01
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
1
Fiscal Year
2005
Total Cost
$57,536
Indirect Cost
Name
Baylor College of Medicine
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Corrales, Rosa Maria; de Paiva, Cintia Sade; Li, De-Quan et al. (2011) Entrapment of conjunctival goblet cells by desiccation-induced cornification. Invest Ophthalmol Vis Sci 52:3492-9
De Paiva, Cintia S; Yoon, Kyung-Chul; Pangelinan, Solherny B et al. (2009) Cleavage of functional IL-2 receptor alpha chain (CD25) from murine corneal and conjunctival epithelia by MMP-9. J Inflamm (Lond) 6:31
De Paiva, Cintia S; Pangelinan, Solherny B; Chang, Emmanuel et al. (2009) Essential role for c-Jun N-terminal kinase 2 in corneal epithelial response to desiccating stress. Arch Ophthalmol 127:1625-31
Pflugfelder, Stephen C; de Paiva, Cintia S; Li, De-Quan et al. (2008) Epithelial-immune cell interaction in dry eye. Cornea 27 Suppl 1:S9-11
Beardsley, Robert M; De Paiva, Cintia S; Power, David F et al. (2008) Desiccating stress decreases apical corneal epithelial cell size--modulation by the metalloproteinase inhibitor doxycycline. Cornea 27:935-40
De Paiva, Cintia S; Villarreal, Arturo L; Corrales, Rosa M et al. (2007) Dry eye-induced conjunctival epithelial squamous metaplasia is modulated by interferon-gamma. Invest Ophthalmol Vis Sci 48:2553-60
De Paiva, Cintia S; Corrales, Rosa M; Villarreal, Arturo L et al. (2006) Apical corneal barrier disruption in experimental murine dry eye is abrogated by methylprednisolone and doxycycline. Invest Ophthalmol Vis Sci 47:2847-56
Corrales, Rosa M; Stern, Michael E; De Paiva, Cintia S et al. (2006) Desiccating stress stimulates expression of matrix metalloproteinases by the corneal epithelium. Invest Ophthalmol Vis Sci 47:3293-302