Retinal localization and copper-dependent relocalization of the Wilson and Menkes disease proteins.
OBJECTIVE
Menkes and Wilson diseases are associated with retinal degeneration. The Menkes and Wilson genes are homologous copper transporters, but differences in their expression pattern lead to different disease manifestations. To determine whether the Wilson and Menkes genes may act locally in the retina, this study was undertaken to assess retinal Wilson and Menkes expression and localization.


METHODS
RT/PCR was used to test for the presence of Wilson and Menkes mRNAs in mouse and human retinas and retinal pigment epithelial cell lines. The Menkes and Wilson proteins were immunolocalized in human and mouse retinas and in the ARPE-19 cell line.


RESULTS
The Menkes mRNA and protein were present in the RPE and neurosensory retina whereas the Wilson mRNA and protein were limited to the RPE. In the RPE, both proteins localized to the Golgi. Increased copper concentration led to relocalization of the Wilson protein to a diffuse cytoplasmic distribution.


CONCLUSIONS
Both the Menkes and Wilson proteins are present in the RPE. Since the RPE is a blood-brain barrier, these proteins most likely regulate not only their own copper levels but also copper levels of the overlying photoreceptors. Because the Wilson protein delivers copper to the ferroxidase ceruloplasmin in the liver, it is likely that the Wilson and/or Menkes proteins provide copper to ceruloplasmin made in the RPE. Retinopathy in Wilson and Menkes diseases may result not only from abnormal systemic copper levels but also from loss of retinal Wilson or Menkes protein.
Krajacic
Predrag
P
F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Qian
Ying
Y
Hahn
Paul
P
Dentchev
Tzvete
T
Lukinova
Nina
N
Dunaief
Joshua L
JL
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000369:Aged, 80 and over; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D017931:DNA Primers / Q000737:chemistry; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D027682:Cation Transport Proteins; D017931:DNA Primers; D012333:RNA, Messenger; D003300:Copper; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases