Retinal function and structure in Ant1-deficient mice.
OBJECTIVE
Mutations in ANT, a mitochondrial ATP transporter, are typically associated with myopathy. Because of the high metabolic demands of the retina, the authors examined whether elimination of the Ant1 isoform in a transgenic mouse affects retinal function or morphology.


METHODS
RT-PCR was used to confirm Ant1 expression in retinas of wild-type (WT) or Ant1(-/-) mice. Full-field ERGs were used to test retinal function under dark- and light-adapted conditions and the recovery of the photoresponse to a bright flash. Using histologic methods, the authors assessed the retinal location of ANT and ANT1-β-gal reporter protein, mitochondrial activity with cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) staining, retinal layer thickness, and bipolar cell types using Chx10 and recoverin.


RESULTS
Ant1(-/-) mice had supernormal ERG b-waves under both dark- and light-adapted conditions. X-Gal staining was detected in a subset of cells within the inner retina. The following characteristics were normal in Ant1(-/-) mice compared with age-matched WT mice: recovery of the photoresponse, COX and SDH activity, retinal morphology, and bipolar cell morphology.


CONCLUSIONS
The presence of ANT1 in a subset of inner retinal cells accompanied by supernormal ERG responses suggests that ANT1 may be localized to hyperpolarizing bipolar cells. However, the immunohistochemical techniques used here did not show any differences in bipolar cells. Moderate functional changes coupled with a lack of detectable morphologic changes suggest that ANT1 is not essential for ATP transport in the retina.
Phillips
M Joseph
MJ
Rehabilitation Research and Development Center, Atlanta VA Medical Center, Decatur, GA 30033, USA.
Webb-Wood
Sarah
S
Faulkner
Amanda E
AE
Jabbar
Seema B
SB
Biousse
Valerie
V
Newman
Nancy J
NJ
Do
Vi T
VT
Boatright
Jeffrey H
JH
Wallace
Douglas C
DC
Pardue
Machelle T
MT
D033741:Adenine Nucleotide Translocator 1 / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D003623:Dark Adaptation; D003576:Electron Transport Complex IV / Q000378:metabolism; D004596:Electroretinography; D007124:Immunoenzyme Techniques; D007625:Kearns-Sayre Syndrome / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D010775:Photic Stimulation; D020033:Protein Isoforms / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D012160:Retina / Q000166:cytology* / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013385:Succinate Dehydrogenase / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D033741:Adenine Nucleotide Translocator 1; D020033:Protein Isoforms; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV; D001616:beta-Galactosidase