Abstract
Abstract: :
Purpose: To study the effect of erythropoietin, a potential neuroprotector, on inherited– and light–induced retinal degeneration in rat models. Methods: In a first set of experiments, dystrophic and control RCS rats were raised in dim–cyclic light. Rats from each group were injected with water or rhEPO (5000 IU/Kg, IP, 3 times/week) starting at postnatal day 22 (P22) to P55. Electroretinograms (ERGs) were recorded at P21, P29, P35, P42, P49 and P55. Histologic analysis was done at P55. In a second set of experiments, wistar rats were raised in dim cyclic light. They were injected with water or rhEPO (5000 IU/Kg or 30000 IU/Kg, IP) and then either exposed for 24 hours at 1700 lux–light or unexposed. ERGs were recorded before treatment or exposure and 1 day after light–exposure. They were sacrificed 10 days later for histologic analysis. For EPO dosage in blood and retinas, wistar rats were injected with rhEPO (5000 IU/Kg, IP) and sacrificed 2, 4, 8 and 24 hours later. Results: In control RCS rats, the maximal b–wave amplitude (Bmax) did not vary significantly between P21 and P55. At P21, dystrophic RCS rats had a maximal b–wave amplitude 35% lower than the control. At P29, they had a Bmax 67% lower than the age–matched control. There was no further decrease thereafter. RhEPO injections had no significant effect on Bmax in control or dystrophic RCS rats. In the second set of experiment, Bmax was significantly reduced to 54% in the untreated light–exposed rats. RhEPO injected at 5000 UI/kg did not have any protective effect but an injection at 30000 UI/kg preserved Bmax to 73%. Erythropoietin dosage showed that rhEPO increased in the plasma at 2 hours up to 24 hours after IP injection and got into the retinas. Conclusions:Although rhEPO injection at 5000 UI/kg induced an increase in plasmatic and retinal EPO concentration, it did not have any effect on light–induced or inherited RCS retinal degeneration. RhEPO had to be injected at 30000 UI/kg to show a protective effect against light–induced retinal degeneration. These results confirm the neuroprotective properties of erythropoietin known as a hematopoietic growth factor.
Keywords: retinal degenerations: hereditary • neuroprotection • electrophysiology: non–clinical