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. In order to understand the mechanism(s) of oxidative damage to the retina, we have investigated the gene expression in the retina of rats exposed to intense visible light. The expression of heme oxygenase-1 (HO-1), a marker for oxidative stress, in the retina is highly increased following light exposure. The expression of HO-1 mRNA in the retina in response to acute intense light was investigated as a function of age in dim cyclic light reared and dark reared rats. The HO-1 mRNA in the retina of treated rats was analyzed by Northern blotting. The intense light exposure markedly increased the HO-1 mRNA expression in the retina irrespective of the rearing environment. However, the response was more pronounced in the dark reared rats. The HO-1 induction increased with age in both dim cyclic light reared and dark reared rats. The increase in HO-1 mRNA is accompanied by apoptotic photoreceptor cell loss. DMTU, an antioxidant, was highly effective in blocking HO-1 induction and photoreceptor cell loss resulting from the intense light exposure. The age or rearing light conditions did not influence the DMTU effect. Thus, age, light history, and antioxidant status are important factors affecting the retinal gene expression in response to stress. Activin, a member of transforming growth factor-beta superfamily, is known to be expressed in the vertebrate retina. We have identified the first invertebrate activin gene from Drosophila. A genomic clone representing 102 F region of Drosophila chromosome 4 was found to encode a putative activin b. The predicted protein sequence showed a multibasic protease site that would generate a mature 113 amino acid C-terminal peptide having more than 60% similarity to vertebrate activin bB. A TGF-b family signature as well as 9 cysteine residues conserved in the vertebrate activins were also present in the mature peptide sequence. The gene was expressed in embryo, larva and adult stages of Drosophila.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000308-04
Application #
6106861
Study Section
Special Emphasis Panel (LRCM)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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