title: Localization of acetylcholine-related molecules in the retina: implication of the communication from photoreceptor to retinal pigment epithelium.
abstract: It has been long speculated that specific signals are transmitted from photoreceptors to the retinal pigment epithelium (RPE). However, such signals have not been identified. In this study, we examined the retinal expression and localization of acetylcholine-related molecules as putative candidates for these signals. Previous reports revealed that α7 nicotinic acetylcholine receptors (nAChRs) are present in the microvilli of RPE cells that envelope the tips of photoreceptor outer segments (OS). Secreted mammalian leukocyte antigen 6/urokinase-type plasminogen activator receptor-related protein-1 (SLURP-1) is a positive allosteric modulator of the α7 nAChR. Therefore, we first focused on the expression of SLURP-1. SLURP-1 mRNA was expressed in the outer nuclear layer, which is comprised of photoreceptor cell bodies. SLURP-1 immunoreactivity co-localized with rhodopsin and S-opsin in photoreceptor OS, while choline acetyltransferase (ChAT) and high affinity choline transporter (CHT-1) were also expressed in photoreceptor OS. Immunoelectron microscopy identified that the majority of SLURP-1 was localized to the plasma membranes of photoreceptor OS. These results provide evidence that SLURP-1 is synthesized in photoreceptor cell bodies and transported to photoreceptor OS, where SLURP-1 may also be secreted. Our findings suggest that photoreceptor OS communicate via neurotransmitters such as ACh and SLURP-1, while RPE cells might receive these signals through α7 nAChRs in their microvilli.
authors.affiliation: Department of Ophthalmology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. hide-m@showa.gunma-u.ac.jp
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Koji
authors.initials: K
authors.lastname: Shibasaki
authors.forename: Motokazu
authors.initials: M
authors.lastname: Uchigashima
authors.forename: Amane
authors.initials: A
authors.lastname: Koizumi
authors.forename: Masashi
authors.initials: M
authors.lastname: Kurachi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Moriwaki
authors.forename: Hidemi
authors.initials: H
authors.lastname: Misawa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kawashima
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Shoji
authors.initials: S
authors.lastname: Kishi
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Ishizaki
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000495:Allosteric Site; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism / Q000648:ultrastructure; D001692:Biological Transport; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003623:Dark Adaptation; D017403:In Situ Hybridization; D008024:Ligands; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000648:ultrastructure; D011950:Receptors, Cholinergic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D055214:Retinal Photoreceptor Cell Outer Segment / Q000201:enzymology; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D015398:Signal Transduction; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism / Q000648:ultrastructure; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D000950:Antigens, Ly; C579166:Chrna7 protein, mouse; D008024:Ligands; D026901:Membrane Transport Proteins; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; C545249:SLURP-1 protein, mouse; D064569:alpha7 Nicotinic Acetylcholine Receptor; C065637:choline transporter; D002795:Choline O-Acetyltransferase; D014568:Urokinase-Type Plasminogen Activator; D000109:Acetylcholine