Location of CNTFRalpha on outer segments: evidence of the site of action of CNTF in rat retina.

Ciliary neurotrophic factor (CNTF) is an important factor in the retina's mechanisms of self-protection. It is generated by retinal glial cells in response to stress, and has a significant protective effect on retinal neurones. In this study we have identified the location of the alpha component of the CNTF receptor complex (CNTFRalpha) in rat retina, using immunohistochemistry and high-resolution confocal microscopy. The major location of CNTFRalpha is on photoreceptor outer segments. More scattered, granular forms of CNTFRalpha were identified in association with Müller cell processes in other retinal layers. Colocalisation of CNTF with CNTFRalpha, suggestive of ligand-receptor binding, was detected on outer segments, and in both normal retinas and retinas stressed by light or oxygen. Results provide evidence that the principal site of CNTF action is the outer segments of photoreceptors. This confirms the known ability of CNTF to protect photoreceptors against stress, and suggest that it acts by modulating mechanisms specific to the outer segment, such as the phototransduction cascade or the membrane channels, which control dark current.