July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Transcriptional comparison of developing and developed human macular retina and RPE-choroid.
Author Affiliations & Notes
  • Andrew P Voigt
    Institute for Vision Research, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • S. Scott whitmore
    Institute for Vision Research, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Megan J Riker
    Institute for Vision Research, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Katayoun Varzavand
    Institute for Vision Research, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Todd E Scheetz
    Institute for Vision Research, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Edwin M Stone
    Institute for Vision Research, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Budd Tucker
    Institute for Vision Research, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Robert F Mullins
    Institute for Vision Research, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Footnotes
    Commercial Relationships   Andrew Voigt, None; S. whitmore, None; Megan Riker, None; Katayoun Varzavand, None; Todd Scheetz, None; Edwin Stone, None; Budd Tucker, None; Robert Mullins, None
  • Footnotes
    Support  NIH Grant EY027038, NIH Grant EY025580
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6010. doi:https://doi.org/
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      Andrew P Voigt, S. Scott whitmore, Megan J Riker, Katayoun Varzavand, Todd E Scheetz, Edwin M Stone, Budd Tucker, Robert F Mullins; Transcriptional comparison of developing and developed human macular retina and RPE-choroid.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6010. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Development of the human retina begins in the first trimester and continues for several months postnatally. For example, the fovea centralis can be identified histologically by 13 weeks of gestation, yet cell migration and differentiation continue to shape the foveal pit as it reaches maturation around eighteen months of life. However, transcriptional changes that lead to successful macular development remain largely uncharacterized. We set out to quantify gene expression differences between human retinas and underlying RPE-choroid before and after foveal specification using RNA-sequencing.

Methods : Human donor eyes from liveborn infants (ages 34 weeks gestation – 9 months) and adults (ages 61 – 93) were obtained, and tissue was collected from: (A) central RPE-choroid (N = 4 infant, N = 13 adult) and (B) central neural retina (N = 3 infant, N = 2 adult). Total RNA was extracted, and poly-A selected RNA transcripts underwent paired-end sequencing at a length of 75 nucleotides on an Illumina HiSeq2000. Reads were mapped to the human reference genome using STAR, and transcripts quantified with featureCounts. Differential expression was assessed with edgeR, and functional pathway analysis of the differentially expressed genes was performed with WebGestalt.

Results : RNA-seq analysis between infant and adult tissues identified 293 differentially expressed genes in the RPE-choroid (p-value < 0.00001, FDR < 0.001, cpm >2) and 292 differentially expressed genes in the retina (p-value < 0.0005, FDR < 0.05, cpm >2). The majority of differentially expressed genes in RPE-choroid (74%) and retina (58%) had higher expression in infant tissue. Genes with increased expression in infant RPE-choroid were notable for pathway enrichment in (a) focal adhesion (e.g., collagen and laminin genes) and (b) axonal guidance (e.g., EPHA, SEMA3D). Genes with increased expression in infant neural retina were enriched in (a) extracellular matrix-receptor interactions (e.g., collagen genes, reelin) and (b) Wnt signaling pathways (e.g., WNT5A, FZD1).

Conclusions : The developing human retina and RPE-choroid are both transcriptionally unique and are enriched in genes that may be implicated in the organization of specialized retinal architecture, including the fovea centralis. Such transcriptomic profiles will be useful references for stem-cell differentiation of macular retina, RPE, and choroid.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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