Abstract

Altered expression of growth factors or growth factor receptors may be involved in regulating retinal pigmented epithelial (RPE) cell proliferation after injury or in mediating trophic interactions with the adjacent photoreceptors. This application explores the hypotheses that PDGFs and FGFs cause autocrine stimulation of RPE, and that FGFs, but not PDGFs promote survival of retinal neurons in RPE cells. There are three specific aims in this application, and each is explored through a series of specific experiments.
The first aim i s to test the hypothesis that PDGFs play a critical role in growth regulation of the RPE, and are relatively more important than basic FGF (bFGF) in this regard.
The second aim i s to test the hypothesis that bFGF supports the survival of retinal neurons in RPE, particularly after environmental stress, and that they are more important than the PDGFs in this regard.
The third aim i s to test the hypothesis that FGF receptor function is required for photoreceptor development and for their survival.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005951-12
Application #
2159672
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1985-09-30
Project End
1999-09-29
Budget Start
1995-09-30
Budget End
1996-09-29
Support Year
12
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Shen, Jikui; Choy, David F; Yoshida, Tsunehiko et al. (2014) Interleukin-18 has antipermeablity and antiangiogenic activities in the eye: reciprocal suppression with VEGF. J Cell Physiol 229:974-83
Ohnaka, Masayuki; Miki, Katsuaki; Gong, Yuan-Yuan et al. (2012) Long-term expression of glial cell line-derived neurotrophic factor slows, but does not stop retinal degeneration in a model of retinitis pigmentosa. J Neurochem 122:1047-53
Usui, Shinichi; Oveson, Brian C; Iwase, Takeshi et al. (2011) Overexpression of SOD in retina: need for increase in H2O2-detoxifying enzyme in same cellular compartment. Free Radic Biol Med 51:1347-54
Oveson, Brian C; Iwase, Takeshi; Hackett, Sean F et al. (2011) Constituents of bile, bilirubin and TUDCA, protect against oxidative stress-induced retinal degeneration. J Neurochem 116:144-53
Dong, Aling; Xie, Bing; Shen, Jikui et al. (2009) Oxidative stress promotes ocular neovascularization. J Cell Physiol 219:544-52
Lu, Lili; Oveson, Brain C; Jo, Young-Joon et al. (2009) Increased expression of glutathione peroxidase 4 strongly protects retina from oxidative damage. Antioxid Redox Signal 11:715-24
Usui, Shinichi; Oveson, Brian C; Lee, Sun Young et al. (2009) NADPH oxidase plays a central role in cone cell death in retinitis pigmentosa. J Neurochem 110:1028-37
Usui, Shinichi; Komeima, Keiichi; Lee, Sun Young et al. (2009) Increased expression of catalase and superoxide dismutase 2 reduces cone cell death in retinitis pigmentosa. Mol Ther 17:778-86
Komeima, Keiichi; Usui, Shinichi; Shen, Jikui et al. (2008) Blockade of neuronal nitric oxide synthase reduces cone cell death in a model of retinitis pigmentosa. Free Radic Biol Med 45:905-12
Chowers, Itay; Wong, Robert; Dentchev, Tzvete et al. (2006) The iron carrier transferrin is upregulated in retinas from patients with age-related macular degeneration. Invest Ophthalmol Vis Sci 47:2135-40