Developmental profile of erythropoietin and its receptor in guinea-pig retina

Evidence suggests that endogenous erythropoietin (EPO) is involved in the development of the central nervous system; however, its role in retinal development is yet to be determined. In this study, we have used fluorescence immunohistochemistry to localise EPO and its receptor (EPOR) in the developing and mature retina of the guinea-pig, a species in which retinal development is similar to that in humans. EPO immunoreactivity (IR) was observed in ganglion cells from 25 days of gestation (dg; term ∼67 dg), and in the inner and outer plexiform layers and in horizontal cells by 40 dg. EPO-IR persisted in all of these structures into adulthood. Müller cells also displayed EPO-IR, which was seen in the radial processes and endfeet at 40 dg and in the cytoplasm by 50 dg. IR in these cells was particularly intense and appeared to increase with age. EPOR-IR was found in all ages examined; it was detected in ganglion cells at 25 dg and, from 30 dg onwards, was localised on, and adjacent to, the cell surface membrane. The distribution of EPOR-IR became increasingly widespread during gestation and, by 50 dg, EPOR-IR was detectable on the majority of retinal somal membranes. This localisation persisted in the postnatal and adult retina. Therefore, IR for EPO and its receptor is present in the guinea-pig retina from as early as 25 dg, when retinal layers are forming, and persists throughout postnatal development. This suggests that EPO plays a role both in retinal development and in the maintenance of the adult retina. This study was funded by the ANZ Charitable Trust; Medical Research and Technology in Victoria (M. Tolcos) and the National Health and Medical Research Council of Australia (M. Tolcos).