title: Downregulation of cone-specific gene expression and degeneration of cone photoreceptors in the Rpe65-/- mouse at early ages.
abstract: OBJECTIVE
  RPE65 is essential for the generation of 11-cis retinal. Rod photoreceptors in the RPE65-knockout (Rpe65(-/-)) mouse are known to degenerate slowly with age. This study was designed to examine cone photoreceptors and the expression of cone-specific genes in the Rpe65(-/-) mouse.
  
  
  METHODS
  Gene expression changes were identified by microarray and confirmed by real-time RT-PCR. Cone photoreceptors were stained by peanut agglutinin (PNA) lectin in the flatmounted retina. The 9- or 11-cis retinal was supplied by intraperitoneal injections.
  
  
  RESULTS
  The short-wavelength (SWL) cone opsin mRNA was markedly decreased at 2 weeks of age, whereas the decrease in the middle-wavelength (MWL) cone opsin mRNA occurred relatively later in age. In contrast, the rhodopsin mRNA level did not show any significant change at all the ages analyzed. Consistent with the cone opsin changes, the cone transducin alpha-subunit mRNA decreased at both 4 and 8 weeks of age, whereas again the rod transducin alpha-subunit did not show any significant change. Rpe65(-/-) mice showed significant cone loss in both the central and ventral retina between 2 and 3 weeks of age. Administration of 9- or 11-cis retinal to Rpe65(-/-) mice 2 weeks of age increased cone density by twofold in these areas.
  
  
  CONCLUSIONS
  In the Rpe65(-/-) mouse, the expression of cone-specific genes is downregulated and is accompanied by cone degeneration at early ages. Early administration of 9- or 11-cis retinal can partially prevent cone loss, suggesting that the absence of 11-cis chromophore may be responsible for the early cone degeneration.
authors.affiliation: Departments of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Sergey L
authors.initials: SL
authors.lastname: Znoiko
authors.forename: Baerbel
authors.initials: B
authors.lastname: Rohrer
authors.forename: Kangmo
authors.initials: K
authors.lastname: Lu
authors.forename: Heather R
authors.initials: HR
authors.lastname: Lohr
authors.forename: Rosalie K
authors.initials: RK
authors.lastname: Crouch
authors.forename: Jian-Xing
authors.initials: JX
authors.lastname: Ma
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D002452:Cell Count; D004224:Diterpenes; D015536:Down-Regulation; D005136:Eye Proteins; D044385:GTP-Binding Protein alpha Subunits; D015870:Gene Expression; D020869:Gene Expression Profiling; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D012162:Retinal Degeneration / Q000378:metabolism*; D012172:Retinaldehyde / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012243:Rhodopsin / Q000235:genetics; D017299:Rod Opsins / Q000235:genetics*; D015293:Transducin / Q000235:genetics; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D004224:Diterpenes; D005136:Eye Proteins; D044385:GTP-Binding Protein alpha Subunits; D020962:Heterotrimeric GTP-Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; D012172:Retinaldehyde; D012243:Rhodopsin; D017299:Rod Opsins; D015293:Transducin; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C488949:Gnat1 protein, mouse; C031338:13-cis-retinal; C031390:9-cis-retinal