The retina of the premature infant is believed to be highly susceptible to damaging influences of oxygen. The reason for this susceptibility is unknown, but it may be the result of an incompletely developed retinal antioxidant system. It has been shown that one antioxidant, heme oxygenase-1 (HO-1), is not developed in the rat until close to the time of birth. It is planned to investigate the kinetics of expression of the major antioxidant systems in the embryonic and neonatal rat retina using in situ hybridizations and ribonuclease protection assays. The importance of HO-1 in protection against oxidative stress will be determined in transgenic mice in which the HO-1 gene is under the control of a switchable promotor and in HO-1 knockout mice. Control of the expression of this enzyme a few days prior to birth will be studied using transgenic mice that carry a reporter gene coupled to the HO-1 promotor. Progressive deletion of the control regions of the promotor will allow the identification of the control sites and transcription factors involved. The identification of such factors may allow the elucidation of signaling pathways that mediate the correct expression of HO-1.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY010516-05
Application #
2859250
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1994-06-01
Project End
2002-05-31
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of South Carolina at Columbia
Department
Pathology
Type
Schools of Medicine
DUNS #
111310249
City
Columbia
State
SC
Country
United States
Zip Code
29208
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Shipulina, N; Hunt, R C; Shaklai, N et al. (1998) Coordination of nitric oxide by heme-hemopexin. J Protein Chem 17:255-60

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