title: OPA1, the disease gene for autosomal dominant optic atrophy, is specifically expressed in ganglion cells and intrinsic neurons of the retina.
abstract: OBJECTIVE
  Autosomal dominant optic atrophy is a hereditary disorder characterized by progressive loss of vision and caused by mutations in a dynamin-related gene, OPA1, which translates into a protein with a mitochondrial leader sequence. In this study the OPA1 gene and its protein were localized in the rat and mouse retina, and its rat orthologue, rOpa1, was identified.
  
  
  METHODS
  The rOpa1 cDNA was isolated by using reverse transcribed cDNA from total RNA obtained from a rat retinal ganglion cell line. The spatial and temporal expression patterns of OPA1 and its gene product were investigated by RNA in situ hybridization and immunohistochemistry in mouse and rat retinas. To characterize further the OPA1-positive neurons, retinal ganglion cells were retrogradely labeled by an immunogold fluorescent tracer or double labeled with OPA1 and choline acetyltransferase or calbindin antibodies.
  
  
  RESULTS
  Protein sequence alignment revealed a 96% identity between rat and human OPA1 mRNA. OPA1 expression was found as early as postnatal day 3 in the developing rodent retina. In the mature retina, the OPA1 gene and its protein were found not only in retinal ganglion cells, but also in starburst amacrine cells and horizontal cells, both of which are involved in lateral signal processing within the retina. However, OPA1 was absent from mitochondria rich nerve fibers and photoreceptor indicating a specific role for OPA1 in signal processing rather than in the requirement of mitochondrial energy supply in the retina.
  
  
  CONCLUSIONS
  The data suggest an important and specific function of the OPA1 protein, not only in the optic nerve forming ganglion cells but also in the intrinsic signal processing of the inner retina.
authors.affiliation: Laboratory of Molecular Genetics, University Eye Hospital, Tübingen, Germany.
authors.forename: Ulrike E A
authors.initials: UE
authors.lastname: Pesch
authors.forename: Julia E
authors.initials: JE
authors.lastname: Fries
authors.forename: Stefanie
authors.initials: S
authors.lastname: Bette
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
authors.forename: Christiane
authors.initials: C
authors.lastname: Alexander
authors.forename: Konrad
authors.initials: K
authors.lastname: Kohler
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003001:Cloning, Molecular; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D029241:Optic Atrophy, Autosomal Dominant / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D020558:GTP Phosphohydrolases; C498809:Opa1 protein, mouse; C498811:Opa1 protein, rat