Journal article
The nuclear receptor NR2E3 plays a role in human retinal photoreceptor differentiation and degeneration
Proceedings of the National Academy of Sciences - PNAS, Vol.99(1), pp.473-478
01/08/2002
DOI: 10.1073/pnas.022533099
PMCID: PMC117584
PMID: 11773633
Abstract
Normal human retinal development involves orderly generation of rods and cones by complex mechanisms. Cell-fate specification involves progenitor cell lineage and external signals such as soluble factors and cell-cell interactions. In most inherited human retinal degenerations, including retinitis pigmentosa, a mutant gene causes loss of visual function, death of mature rods, and eventually death of all cone subtypes. Only one inherited retinal disorder, the enhanced S cone syndrome (ESCS), shows increased visual function, involving the minority S (blue) cones, and decreased rod and L/M (red/green) cone function. This autosomal recessive disease is caused by mutations in NR2E3, a photoreceptor nuclear receptor transcription factor, and may result from abnormal cell-fate determination, leading to excess S cones at the expense of other photoreceptor subtypes. In 16 ESCS patients with the most common NR2E3 mutation, R311Q, we documented an abnormal ratio of S to L/M cone function and progressive retinal degeneration. We studied the postmortem retina of an ESCS patient homozygous for NR2E3 R311Q. No rods were identified, but cones were increased approximately 2-fold, and 92% were S cones. Only 15% of the cones expressed L/M cone opsin, and some coexpressed S cone opsin. The retina was disorganized, with densely packed cones intermixed with inner retinal neurons. The retina was also degenerate, retaining photoreceptors in only the central and far peripheral regions. These observations suggest a key role for NR2E3 in regulation of human photoreceptor development. Degeneration of the NR2E3 retina may result from defective development, known S cone fragility, or abnormal maintenance of mature photoreceptors.
Details
- Title: Subtitle
- The nuclear receptor NR2E3 plays a role in human retinal photoreceptor differentiation and degeneration
- Creators
- Ann H Milam - Scheie Eye Institute and F. M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA. annmilam@mail.med.upenn.eduLinda RoseArtur V CideciyanMark R BarakatWai-Xing TangNisha GuptaTomas S AlemanAlan F WrightEdwin M StoneVal C SheffieldSamuel G Jacobson
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.99(1), pp.473-478
- DOI
- 10.1073/pnas.022533099
- PMID
- 11773633
- PMCID
- PMC117584
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- United States
- Grant note
- R01 EY013203 / NEI NIH HHS EY-05627 / NEI NIH HHS EY-13203 / NEI NIH HHS
- Language
- English
- Date published
- 01/08/2002
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980067602771
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