Epithelial cell adhesion to the basal lamina and the formation of hemidesmosomes is critical to the health and integrity of the cornea. Hemidesmosomes are root-like structures along the basal surface and bridge the epithelium and stromal matrix. Hyperplasia and/or faulty adhesion of epithelium may be caused by various diseases or trauma such as chemical or thermal burns. The overall goal of this proposal is to determine how injury and the subsequent release of cellular factors induces changes in migration and the assembly and/or disassembly of hemidesmosomes. Specifically, the aims of the project are to 1) isolate and determine the hierarchy of injury-induced signal transduction mediated events in the corneal epithelium; 2) characterize the role of specific hemidesmosome proteins; and 3) define the role of growth factors on the integrity of hemidesmosomes and their transition to migratory structures. The adhesion and wound models developed by the applicant will be used to examine these interactions. To achieve these aims, the applicant will use live cell imaging of wounds and analyze the expression of adhesion receptors and hemidesmosome proteins at specific intervals. The responses will be correlated with changes in protein localization and hemidesmosome formation. A better understanding of the factors that control the normal wound repair process will provide important insight into the treatment of epithelial disorders.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
3R01EY006000-17S1
Application #
6775288
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Fisher, Richard S
Project Start
1986-06-01
Project End
2004-05-31
Budget Start
2002-06-01
Budget End
2004-05-31
Support Year
17
Fiscal Year
2003
Total Cost
$198,238
Indirect Cost
Name
Boston University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Lee, Albert; Karamichos, Dimitrios; Onochie, Obianamma E et al. (2018) Hypoxia modulates the development of a corneal stromal matrix model. Exp Eye Res 170:127-137
Kneer, Krisandra; Green, Michael B; Meyer, Jenna et al. (2018) High fat diet induces pre-type 2 diabetes with regional changes in corneal sensory nerves and altered P2X7 expression and localization. Exp Eye Res 175:44-55
Minns, Martin S; Trinkaus-Randall, Vickery (2016) Purinergic Signaling in Corneal Wound Healing: A Tale of 2 Receptors. J Ocul Pharmacol Ther 32:498-503
Minns, Martin S; Teicher, Gregory; Rich, Celeste B et al. (2016) Purinoreceptor P2X7 Regulation of Ca(2+) Mobilization and Cytoskeletal Rearrangement Is Required for Corneal Reepithelialization after Injury. Am J Pathol 186:285-96
Derricks, Kelsey E; Trinkaus-Randall, Vickery; Nugent, Matthew A (2015) Extracellular matrix stiffness modulates VEGF calcium signaling in endothelial cells: individual cell and population analysis. Integr Biol (Camb) 7:1011-25
Karamichos, D; Hutcheon, A E K; Rich, C B et al. (2014) In vitro model suggests oxidative stress involved in keratoconus disease. Sci Rep 4:4608
Lee, Albert; Derricks, Kelsey; Minns, Martin et al. (2014) Hypoxia-induced changes in Ca(2+) mobilization and protein phosphorylation implicated in impaired wound healing. Am J Physiol Cell Physiol 306:C972-85
Sanderson, Julie; Dartt, Darlene A; Trinkaus-Randall, Vickery et al. (2014) Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland. Exp Eye Res 127:270-9
Stepp, Mary Ann; Zieske, James D; Trinkaus-Randall, Vickery et al. (2014) Wounding the cornea to learn how it heals. Exp Eye Res 121:178-93
Chi, Cheryl; Trinkaus-Randall, Vickery (2013) New insights in wound response and repair of epithelium. J Cell Physiol 228:925-9

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