Growth hormone (GH), identical to that in the pituitary, is expressed in retinal ganglion cells (RGCs) in chickens, rats, mice and humans. Retinal GH is a neuroprotective factor, as it stimulates RGC survival and, in humans, the concentration of GH in vitreous fluid may be a marker for ocular disease. Indeed, vitreal GH concentrations are low in diabetic patients that have increased RGC death and glaucoma. Increasing GH expression in RGCs could thus have therapeutic potential in the treatment of glaucoma, which results from RGC death. The factors regulating retinal GH expression are, however, unknown. The possibility that GH-releasing hormone (GHRH) might be involved in the expression of retinal GH was therefore investigated, since hypothalamic GHRH is the primary stimulator of pituitary GH secretion. The possible presence of GHRH was determined by immunohistochemistry, using retinal sections from embryonic chicks and fixed QNR/D cells (a commercial neuroretinal cell line). The possible GH-releasing activity of GHRH was determined by the in vitro culture of QNRD cells with exogenous GHRH and by the measurement of GH mRNA, using of quantitative PCR. GHRH immunoreactivity was abundantly present in the cytoplasm of chick retinal RGCs and in QNR/D cells and in both cases was co-localized with GH immunoreactivity. After a 24h incubation in exogenous GHRH (at 10-6M) GH mRNA in the QNR/D cells was significantly (<P0.05) increased. These results demonstrate, for the first time, that GHRH is present in retinal RGCs and that exogenous GHRH promotes retinal GH expression. The co-localization of GH and GHRH also suggests that retinal GH regulation occurs locally by autocrine or paracrine mechanisms.