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(Investigative Ophthalmology and Visual Science. 2004;45:2807-2812.)
© 2004 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.03-1317

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Expression of Photoreceptor-Specific Nuclear Receptor NR2E3 in Rod Photoreceptors of Fetal Human Retina

Keely M. Bumsted O’Brien,1,2 Hong Cheng,3 Yibin Jiang,4 Dorothea Schulte,1 Anand Swaroop,3,4,5 and Anita E. Hendrickson6,7

1From the Max Planck Institute for Brain Research, Neuroanatomy Department, Frankfurt am Main, Germany; 2Department of Optometry and Vision Science, University of Aukland, Aukland, New Zealand; 3Program in Neuroscience, Departments of 4Ophthalmology and Visual Sciences, and 5Human Genetics, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan; and the Departments of 6Biological Structure and 7Ophthalmology, University of Washington, Seattle, Washington.

PURPOSE. To study the physiological function of NR2E3 and possible molecular mechanisms underlying enhanced short-wavelength cone syndrome (ESCS) pathogenesis in developing human retina, and to compare its expression to that of Neural Retina Leucine zipper (NRL), a transcription factor essential for rod differentiation.

METHODS. Expression of NR2E3, a photoreceptor-specific orphan nuclear receptor, was examined in human retinas between fetal weeks (Fwk) 9 to 22 by reverse transcription–polymerase chain reaction (RT-PCR) and in situ hybridization. Both NR2E3 and NRL expression patterns were followed by immunocytochemistry. The human retina develops in a central to peripheral pattern, in which a protein may take weeks to be expressed throughout the entire retina. This allowed a detailed temporal analysis of NR2E3 and NRL expression.

RESULTS. NR2E3 expression was detected shortly after the appearance of NRL in putative immature rods on the foveal edge at Fwk 11.7. Expression of both markers was maintained in rod opsin expressing fetal photoreceptors. NR2E3 expression was not detected in either long/medium- or short-wavelength cones. Its absence from cones was also supported by the position of labeled nuclei deep in the outer nuclear layer, and by the absence of NR2E3 from the fovea.

CONCLUSIONS. A role for NR2E3 in the rod developmental pathway is suggested. The closely related expression patterns of NRL and NR2E3 supported an interactive function, where both transcription factors determine the rod fate and suppress immature rods from adopting the S-cone fate.





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