Neuroprotection by Erythropoietin: Doping for the Eye
Grimm C.1, Wenzel A.1, Groszer M.2, Seeliger M.3, Mayser H.3, Gassmann M.4, Remé C. E.1
1Lab of Retinal Cell Biology, University Hospital Zurich, Switzerland; 2 UCLA Los Angeles, USA; 3University Tuebingen, Germany; 4Department of Physiology, University of Zurich, Switzerland
Purpose: To investigate the neuroprotective potential of erythropoietin in induced and inherited retinal degeneration.
Method: Groups of mice were exposed to reduced oxygen concentrations (hypoxia) for 6 hours or were kept normoxic. The molecular hypoxic response of the retina was analyzed biochemically after various periods of reoxygenation. Gene expression was tested by real-time or by exponential PCR. Western blotting and immunohistochemistry was used to analyze retinal proteins. The neuroprotective capacity of endogenous (by hypoxic elevation) or exogenous (intraperitoneal injection of recombinant human, rh) EPO was tested in an acute light damage system. Levels of apoptosis induced by the light exposure were analyzed using morphological sections or by an ELISA assay measuring the amount of free nucleosomes in cytoplasmic retinal extracts. The effect of high EPO levels on inherited retinal degeneration was tested by introducing a highly expressed Epo transgene (tg6) into the rd mouse. Retinal morphology was assessed at postnatal day 11, 21 and 37.
Results: Hypoxic exposure transiently stabilized hypoxia inducible f
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