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Carboxypeptidase E is required for normal synaptic transmission from photoreceptors to the inner retina
Author(s) -
Zhu Xuemei,
Wu Kebin,
Rife Lawrence,
Cawley Niamh X.,
Brown Bruce,
Adams Tiffany,
Teofilo Karen,
Lillo Concepcion,
Williams David S.,
Loh Y. Peng,
Craft Cheryl M.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03460.x
Subject(s) - retina , erg , electroretinography , neurotransmission , retinal , biology , synapse , retinal degeneration , synaptic vesicle , endocrinology , medicine , microbiology and biotechnology , anatomy , neuroscience , biochemistry , vesicle , receptor , membrane
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.