Carboxypeptidase E is required for normal synaptic transmission from photoreceptors to the inner retina.
Defects in the gene encoding carboxypeptidase E (CPE) in either mouse or human lead to multiple endocrine disorders, including obesity and diabetes. Recent studies on Cpe-/- mice indicated neurological deficits in these animals. As a model system to study the potential role of CPE in neurophysiology, we carried out electroretinography (ERG) and retinal morphological studies on Cpe-/- and Cpe fat/fat mutant mice. Normal retinal morphology was observed by light microscopy in both Cpe-/- and Cpe(fat/fat) mice. However, with increasing age, abnormal retinal function was revealed by ERG. Both Cpe-/- and Cpe fat/fat animals had progressively reduced ERG response sensitivity, decreased b-wave amplitude and delayed implicit time with age, while maintaining a normal a-wave amplitude. Immunohistochemical staining showed specific localization of CPE in photoreceptor synaptic terminals in wild-type (WT) mice, but in both Cpe-/- and Cpe fat/fat mice, CPE was absent in this layer. Bipolar cell morphology and distribution were normal in these mutant mice. Electron microscopy of retinas from Cpe fat/fat mice revealed significantly reduced spherule size, but normal synaptic ribbons and synaptic vesicle density, implicating a reduction in total number of vesicles per synapse in the photoreceptors of these animals. These results suggest that CPE is required for normal-sized photoreceptor synaptic terminal and normal signal transmission to the inner retina.
Zhu
Xuemei
X
The Mary D. Allen Laboratory for Vision Research, Doheny Eye Institute, and Departmentsof Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA. xuemeizh@usc.edu
Wu
Kebin
K
Rife
Lawrence
L
Cawley
Niamh X
NX
Brown
Bruce
B
Adams
Tiffany
T
Teofilo
Karen
K
Lillo
Concepcion
C
Williams
David S
DS
Loh
Y Peng
YP
Craft
Cheryl M
CM
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern / Q000379:methods; D043423:Carboxypeptidase H / Q000172:deficiency / Q000502:physiology*; D004596:Electroretinography / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009154:Mutation; D010786:Photoreceptor Cells / Q000502:physiology* / Q000648:ultrastructure; D051571:Protein Kinase C-alpha / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012160:Retina / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013569:Synapses / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*
D012333:RNA, Messenger; D051571:Protein Kinase C-alpha; D043423:Carboxypeptidase H