Oxidative stress is thought to be a major contributor to the development of retinal degenerative disorders such as macular degeneration, retinopathy of prematurity, and diabetic retinopathy. To understand the mechanism(s) of oxidative damage to the retina, we have investigated the gene expression in the retina and retinal pigment epithelium (RPE) in response to oxidative stress. Agents causing oxidative stress such as metal ions (cadmium, mercury, and cobalt), menadione, sodium arsenite, heme, and iodoacetamide greatly increased the expression of the inducible heme oxygenase (HO-1, HSP32) in human RPE cells in culture. The increased expression of HO-1 is considered to be a cellular defense against oxidative stress, as it is often accompanied by an increased formation of bilirubin, an excellent antioxidant. The expression of the inducible nitric oxide synthase (iNOS) in these cells is found not to be affected by these agents. The increase in the expression of iNOS is associated with the generation of large amounts of nitric oxide, an agent known to cause oxidative damage. The iNOS expression, however, is highly increased by a combination of cytokines (IFN-3, IL-1beta and TNF-alpha). Although the expression of HO-1 in RPE cells is markedly increased by TGF-beta, the cytokine-mediated increase in the expression of iNOS is effectively blocked by the growth factor. The expression of HO-1 and iNOS is also analyzed in retina samples from rats exposed to bright light. The interaction of light with visual pigments could produce reactive oxygen species injurious to the retina. An unusually large amount of HO-1 mRNA is detected in the retina after the exposure to bright light. However, the iNOS mRNA is not increased by this treatment. The elucidation of the molecular mechanism governing the expression of HO-1, iNOS, and other genes in the retina could lead to a better understanding of various degenerative retinal disorders.
| Organisciak, D T; Darrow, R M; Barsalou, L et al. (2000) Circadian-dependent retinal light damage in rats. Invest Ophthalmol Vis Sci 41:3694-701 |
| Takeda, A; Perry, G; Abraham, N G et al. (2000) Overexpression of heme oxygenase in neuronal cells, the possible interaction with Tau. J Biol Chem 275:5395-9 |
