期刊
JOURNAL OF NEUROSCIENCE
卷 24, 期 25, 页码 5651-5658出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1288-04.2004
关键词
retinal degeneration; erythropoietin; apoptosis; neuroprotection; photoreceptor; transgene
资金
- NCRR NIH HHS [P20 RR017703-01, P20 RR017703, P20 RR 017703] Funding Source: Medline
- NEI NIH HHS [P30 EY012190, EY12190, EY-10609, R01 EY010609, R56 EY010609, R01 EY010609-08, R01 EY010609-07] Funding Source: Medline
Elevation of erythropoietin (Epo) concentrations by hypoxic preconditioning or application of recombinanthuman Epo (huEpo) protects the mouse retina against light-induced degeneration by inhibiting photoreceptor cell apoptosis. Because photoreceptor apoptosis is also the common path to cell loss in retinal dystrophies such as retinitis pigmentosa ( RP), we tested whether high levels of huEpo would reduce apoptotic cell death in two mouse models of human RP. We combined the two respective mutant mouse lines with a transgenic line (tg6) that constitutively overexpresses huEpo mainly in neural tissues. Transgenic expression of huEpo caused constitutively high levels of Epo in the retina and protected photoreceptors against light-induced degeneration; however, the presence of high levels of huEpo did not affect the course or the extent of retinal degeneration in a light-independent (rd1) and a light-accelerated (VPP) mouse model of RP. Similarly, repetitive intraperitoneal injections of recombinant huEpo did not protect the retina in the rd1 and the VPP mouse. Lack of neuroprotection by Epo in the two models of inherited retinal degeneration was not caused by adaptational downregulation of Epo receptor. Our results suggest that apoptotic mechanisms during acute, light-induced photoreceptor cell death differ from those in genetically based retinal degeneration. Therapeutic intervention with cell death in inherited retinal degeneration may therefore require different drugs and treatments.
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