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Exp Eye Res. 2014 Dec;129:93-106. doi: 10.1016/j.exer.2014.11.001. Epub 2014 Nov 5.

Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq.

Author information

1
Stephen A. Wynn Institute for Vision Research, The University of Iowa, Iowa City, IA, USA; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA. Electronic address: steven-whitmore@uiowa.edu.
2
Stephen A. Wynn Institute for Vision Research, The University of Iowa, Iowa City, IA, USA; Department of Biomedical Engineering, College of Engineering, The University of Iowa, Iowa City, IA, USA. Electronic address: alex-wagner@uiowa.edu.
3
Stephen A. Wynn Institute for Vision Research, The University of Iowa, Iowa City, IA, USA; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA. Electronic address: adam-deluca@uiowa.edu.
4
Stephen A. Wynn Institute for Vision Research, The University of Iowa, Iowa City, IA, USA; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA. Electronic address: arlene-drack@uiowa.edu.
5
Stephen A. Wynn Institute for Vision Research, The University of Iowa, Iowa City, IA, USA; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA. Electronic address: edwin-stone@uiowa.edu.
6
Stephen A. Wynn Institute for Vision Research, The University of Iowa, Iowa City, IA, USA; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA. Electronic address: budd-tucker@uiowa.edu.
7
Stephen A. Wynn Institute for Vision Research, The University of Iowa, Iowa City, IA, USA; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA. Electronic address: shemin-zeng@uiowa.edu.
8
Stephen A. Wynn Institute for Vision Research, The University of Iowa, Iowa City, IA, USA; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA; Department of Biomedical Engineering, College of Engineering, The University of Iowa, Iowa City, IA, USA. Electronic address: terry-braun@uiowa.edu.
9
Stephen A. Wynn Institute for Vision Research, The University of Iowa, Iowa City, IA, USA; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA. Electronic address: robert-mullins@uiowa.edu.
10
Stephen A. Wynn Institute for Vision Research, The University of Iowa, Iowa City, IA, USA; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA; Department of Biomedical Engineering, College of Engineering, The University of Iowa, Iowa City, IA, USA. Electronic address: todd-scheetz@uiowa.edu.

Abstract

Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with regional phenotypes.

KEYWORDS:

Choroid; Gene expression; Macular degeneration; RNA-Seq; RPE; Retina; Retinitis pigmentosa; Transcriptome

PMID:
25446321
PMCID:
PMC4259842
DOI:
10.1016/j.exer.2014.11.001
[Indexed for MEDLINE]
Free PMC Article
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