In vivo study of the role of a6-containing nicotinic acetylcholine receptor in retinal function using subtype-specific RDP-MII(E11R) toxin

Although α6-contaning (α6*) nicotinic acetylcholine receptors (nAChRs) are densely expressed in the visual system, their role is not well known. We have characterized a family of toxins that are antagonists for α6β2* receptors and used one of these [RDP-MII(E11R)] to localize α6* nAChRs and investigate their impact on retinal function in adult Long-Evans rats. The α6*nAChRs in retinal tissue were localized using either a fluorescently tagged [RDP-MII(E11R)] or anti-α6-specific antibodies and found to be predominantly at the level of the ganglion cell layer. After intraocular injection of RDP-MII(E11R) in one eye and vehicle or inactive MII in contralateral eyes as controls, we recorded flash electroretinograms (F-ERGs), pattern ERGs (P-ERGs), and cortical visual-evoked potential (VEPs). There was no significant difference in F-ERG between the RDP-MII(E11R)-treated and control eyes. In contrast, P-ERG response amplitude was significantly reduced in the RDP-MII(E11R)-injected eye. Blocking α6* nAChRs at retinal level also decreased the VEP amplitude recorded in the visual cortex contralateral to the injected eye. Because both the cortical and inner retina output were affected by RDP-MII(E11R), whereas photoreceptor output was preserved, we conclude that the reduced visual response was due to an alteration in the function of α6* nAChRs present in the ganglion cell layer.-Barloscio, D., Cerri, E., Domenici, L., Longhi, R., Dallanoce, C., Moretti, M., Vilella, A., Zoli, M., Gotti, C., and Origlia, N. In vivo study of the role of α6-containing nicotinic acetylcholine receptor in retinal function using subtype-specific RDP-MII(E11R) toxin.