July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
What makes the fovea so special?
Author Affiliations & Notes
  • Todd E Scheetz
    University of Iowa, Iowa City, Iowa, United States
    Institute for Vision Research, Iowa, United States
  • Andrew Voigt
    University of Iowa, Iowa City, Iowa, United States
    Institute for Vision Research, Iowa, United States
  • Adam Deluca
    University of Iowa, Iowa City, Iowa, United States
    Institute for Vision Research, Iowa, United States
  • Erin Burnight
    University of Iowa, Iowa City, Iowa, United States
    Institute for Vision Research, Iowa, United States
  • S. Scott whitmore
    University of Iowa, Iowa City, Iowa, United States
    Institute for Vision Research, Iowa, United States
  • Budd Tucker
    University of Iowa, Iowa City, Iowa, United States
    Institute for Vision Research, Iowa, United States
  • Edwin M Stone
    University of Iowa, Iowa City, Iowa, United States
    Institute for Vision Research, Iowa, United States
  • Robert F Mullins
    University of Iowa, Iowa City, Iowa, United States
    Institute for Vision Research, Iowa, United States
  • Footnotes
    Commercial Relationships   Todd Scheetz, None; Andrew Voigt, None; Adam Deluca, None; Erin Burnight, None; S. whitmore, None; Budd Tucker, None; Edwin Stone, None; Robert Mullins, None
  • Footnotes
    Support  NIH Grants EY027038 and EY025580
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6038. doi:https://doi.org/
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      Todd E Scheetz, Andrew Voigt, Adam Deluca, Erin Burnight, S. Scott whitmore, Budd Tucker, Edwin M Stone, Robert F Mullins; What makes the fovea so special?. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6038. doi: https://doi.org/.

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

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Abstract

Purpose : To investigate the transcriptomic differences between the human macular retina and the fovea centralis, which are structurally distinct in morphology, organization, and connection between photoreceptor cells and inner retinal neurons. For reasons that are not well understood, the foveal photoreceptor cells are selectively damaged or selectively spared in different patients and in different macular diseases. The fovea is essential to high-acuity vision, and its recapitulation will be essential in restoring full visual acuity in patients that have lost much of their central vision.

Methods : We obtained concentric 1 mm (foveal), 4 mm (perifoveal), and 8 mm (macular) punches of retina from four human donor eyes without known history of eye disease. NGS libraries were prepared for each of the 12 samples using the Illumina stranded TruSeq protocol. These libraries were pooled and sequenced on an Illumina HiSeq 4500. The resulting sequence data was analyzed using our standard RNA-Seq analysis protocol, including alignment to the human reference genome, identification of differentially expressed transcripts, and evaluation of pathways and functional gene sets (STAR, DE-Seq2, WebGestalt).

Results : We identified 730 genes that were differentially expressed between fovea and macula. A comparison of the first three principal components shows that the perifoveal samples are intermediate between foveal and macular samples (Figure 1). To highlight the expression differences particular to the fovea, we focused on the fovea versus macula analysis when assessing expression changes in pathways and functional gene sets. This analysis showed differential expression in multiple developmental pathways, including those for cytoskeletal organization, morphogenesis of an epithelial fold, and neuron projection increased in fovea; and neurogenesis and retina development increased in macula.

Conclusions : This experiment is an extension of our research to determine the differences in the macular and foveal regions, with the goal of discovering the molecular basis for the preferential preservation or degradation of those regions in different retinal diseases. Based upon the changes in expression, neuronal guidance and cytoskeleton changes are important in modulating or maintaining the structures of the fovea and central macula

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

 

A 3D representation of principal components, showing that the perifoveal samples have an intermediate expression pattern.

A 3D representation of principal components, showing that the perifoveal samples have an intermediate expression pattern.

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