gms | German Medical Science

Introduction: The hormone erythropoietin not only stimulates erythropoiesis, but it also has an effect on other tissues as a general growth and survival factor. rhEPO has been shown to have effective anti-apoptotic, neuro- and cardio-protective activities. The aim of the present study was to evaluate the effect of rhEPO on the ischemia-induced hair cell damage in comparison to the effects of insulin-like growth factor-1 (rhIGF-1) und epidermal growth factor (rhEGF).

Methods: The apical, middle and basal parts of the rat organ of Corti (postnatal days 3-4) were exposed to ischemia in glucose-free artificial perilymph with or without rhEPO (5.2 ng/ml, Roche), rhIGF-1 (50 ng/ml, R&D) and rhEGF (200 ng/ml, R&D) in a Billups chamber for 3.5 h (pO2 = 5-10 mm Hg). 24 h after onset of ischemia, the cultures were stained using TRITC phalloidin (intact inner and outer hair cells), propidium iodide (necrotic nuclei) and oligonucleotides, which identify apoptotic nuclei (in situ DNA End Labeling Assay). The numbers of stained hair cells and nuclei per 100 µm were counted in at least three regions of each cochlear part.

Results: Ischemia without growth factors induced a mean hair cell loss of 20-40% in the middle and basal cochlear parts. rhEPO und rhIGF-1 reduced the hair cell loss by 14% and 27% on average. rhEGF was not effective. Ischemia induced 1-7 necrotic and apoptotic nuclei/100 µm in the three cochlear parts. rhEPO and rhIGF-1 reduced this number by about 50%.

Conclusion: rhEPO and rhIGF-1 attenuate the ischemia-induced hair cell loss by reducing apoptosis and necrosis. rhEPO has been in clinical use for the treatment of anemia and found to be well tolerated. Clinical studies will have to clarify whether rhEPO could be an effective drug for the prevention of hearing loss.