Corneal scars limit vision for hundreds of millions of persons worldwide. Scarring has a diverse etiology but is usually permanent and correctable only by surgery. The long-range goal of this research to determine the physical and biological properties of corneal scar tissue and the conditions that control its formation. Proteoglycans constitute a major component of the stroma and proper proteoglycan composition appears essential for corneal transparency. There is a marked alteration in the proteoglycan composition of scar tissue compared to that of normal tissue; however, the nature of scar proteoglycans is not well defined. A model is presented proposing roles for proteoglycans in the biology of scar tissue based on our current knowledge of extracellular matrix biology. Experiments, testing hypotheses based on this model, are designed to accomplish four specific aims: (1) Compare proteoglycans of normal and scarred human corneas in terms of proteoglycan molecular types. (2) Define specific interactions between corneal proteoglycans and other biochemical components of the corneal extracellular matrix. (3) Examine the biological activity of proteoglycans (4) Determine factors regulating scar tissue synthesis by keratocytes. For the first aim, antibodies will be used to determine the abundance and identity of proteoglycan protein cores in histological sections and in extracts of scarred human corneas. Lectins and antibodies against the carbohydrate portions of these molecules will be used to define their state of glycosylation.
In aim 2 & 3, purified proteoglycans, representative of those identified in scarred and normal stroma, will be examined for specific interactions with extracellular matrix molecules and with cells of scar tissue. Effect of the state of glycosylation and of specific amino acid sequence in the core protein will be assessed by use of deglycosylated proteins and of recombinant-proteins containing portions of the core proteins. Interactions will be examined with collagens, laminin, transforming growth factor beta, keratocytes, and macrophages, assessing proteoglycan binding and the biological effects of the binding. In the fourth aim, a soluble factor affecting keratocyte function will be purified and characterized. These experiments will provide knowledge essential to our understanding of corneal scar biology and to our ability to control this pathological process.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009368-05
Application #
2459138
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1993-08-01
Project End
1998-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Kansas State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Manhattan
State
KS
Country
United States
Zip Code
66506
Syed-Picard, Fatima N; Du, Yiqin; Hertsenberg, Andrew J et al. (2018) Scaffold-free tissue engineering of functional corneal stromal tissue. J Tissue Eng Regen Med 12:59-69
Syed-Picard, Fatima N; Du, Yiqin; Lathrop, Kira L et al. (2015) Dental pulp stem cells: a new cellular resource for corneal stromal regeneration. Stem Cells Transl Med 4:276-85
Wu, Jian; Du, Yiqin; Mann, Mary M et al. (2014) Corneal stromal stem cells versus corneal fibroblasts in generating structurally appropriate corneal stromal tissue. Exp Eye Res 120:71-81
Wu, Jian; Rnjak-Kovacina, Jelena; Du, Yiqin et al. (2014) Corneal stromal bioequivalents secreted on patterned silk substrates. Biomaterials 35:3744-55
Karamichos, Dimitrios; Funderburgh, Martha L; Hutcheon, Audrey E K et al. (2014) A role for topographic cues in the organization of collagenous matrix by corneal fibroblasts and stem cells. PLoS One 9:e86260
Chan, Audrey A; Hertsenberg, Andrew J; Funderburgh, Martha L et al. (2013) Differentiation of human embryonic stem cells into cells with corneal keratocyte phenotype. PLoS One 8:e56831
Roh, Danny S; Du, Yiqin; Gabriele, Michelle L et al. (2013) Age-related dystrophic changes in corneal endothelium from DNA repair-deficient mice. Aging Cell 12:1122-31
Boote, Craig; Du, Yiqin; Morgan, Sian et al. (2012) Quantitative assessment of ultrastructure and light scatter in mouse corneal debridement wounds. Invest Ophthalmol Vis Sci 53:2786-95
Roh, Danny S; Funderburgh, James L (2011) Rapid changes in connexin-43 in response to genotoxic stress stabilize cell-cell communication in corneal endothelium. Invest Ophthalmol Vis Sci 52:5174-82
Du, Yiqin; Roh, Danny S; Funderburgh, Martha L et al. (2010) Adipose-derived stem cells differentiate to keratocytes in vitro. Mol Vis 16:2680-9

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