June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Transcriptome analysis of AMD retina reveals convergent molecular pathology
Author Affiliations & Notes
  • Rinki Ratnapriya
    Neurobiol-Neurodegen & Repair Lab, NEI, Bethesda, Maryland, United States
  • Margaret Risa Starostik
    Neurobiol-Neurodegen & Repair Lab, NEI, Bethesda, Maryland, United States
  • Rebecca Kapphahn
    Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States
  • Ashley Walton
    Neurobiol-Neurodegen & Repair Lab, NEI, Bethesda, Maryland, United States
  • Alexandra Pietraszkiewicz
    Neurobiol-Neurodegen & Repair Lab, NEI, Bethesda, Maryland, United States
  • Matthew Brooks
    Neurobiol-Neurodegen & Repair Lab, NEI, Bethesda, Maryland, United States
  • Sandra Rocio Montezuma
    Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States
  • Lars Fritsche
    Center for Statistical Genetics, Department of Biostatistics, University of Micgigan, Ann Arbor, Michigan, United States
  • Goncalo Abecasis
    Center for Statistical Genetics, Department of Biostatistics, University of Micgigan, Ann Arbor, Michigan, United States
  • Deborah A Ferrington
    Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States
  • Anand Swaroop
    Neurobiol-Neurodegen & Repair Lab, NEI, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Rinki Ratnapriya, None; Margaret Starostik, None; Rebecca Kapphahn, None; Ashley Walton, None; Alexandra Pietraszkiewicz, None; Matthew Brooks, None; Sandra Montezuma, None; Lars Fritsche, None; Goncalo Abecasis, None; Deborah Ferrington, None; Anand Swaroop, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4772. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Rinki Ratnapriya, Margaret Risa Starostik, Rebecca Kapphahn, Ashley Walton, Alexandra Pietraszkiewicz, Matthew Brooks, Sandra Rocio Montezuma, Lars Fritsche, Goncalo Abecasis, Deborah A Ferrington, Anand Swaroop; Transcriptome analysis of AMD retina reveals convergent molecular pathology
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):4772.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : AMD has seen spectacular success in deciphering the genetic underpinnings with 52 common and rare variants at 34 loci identified to date. Yet, the mechanism through which associated variants confer liability has not been extensively explored. Post-GWAS, variation in gene expression regulation has been established as a major basis of complex disease risk. However, a comprehensive analysis of gene expression and regulation in healthy and diseased retina has been lacking in the field. Here we describe transcriptome analysis (RNAseq) and whole genome genotyping of human retinae of over 500 donor retinas at different stages of AMD to address some of these challenges.

Methods : Donor eyes were evaluated for absence/presence and severity of AMD using the Minnesota Grading Systems. Retina samples from 128 controls, 197 early AMD, 126 intermediate AMD and 66 advanced AMD of were analyzed. RNA and DNA was isolated using TRIzol®, libraries were made with the TruSeq® Stranded mRNA Library Preparation Kit and sequencing was performed on the Illumina Hiseq 2500. Reads were aligned to the Ensembl 38.5 using STAR, and RSEM was used to estimate gene- and transcript level quantification. Differential analysis was performed using limma; DAVID and GO was used for pathways analysis. WGCNA was employed to identify discrete gene modules based on co-expressions between genes. Genotyping was generated on a custom-modified HumanCoreExome array, followed by imputation using Haplotype Reference Consortium (HRC) panel on Michigan Imputation Server.

Results : Pathway analysis of differentially expressed genes revealed stage-specific progression of AMD from healthy tissue to advanced stages. Several AMD associated genes, especially those associated with immune response, were up regulated in early stages with later alterations in complement and extracellular matrix pathways. WGCNA analysis identified several co-expression modules in normal and AMD retina. We are currently performing eQTL analysis for evaluating the impact of risk variants on gene regulation to gain novel insights into AMD.

Conclusions : Our data represent the largest resource of gene expression and its genetic regulation in vision research. Our findings highlight the genes, pathways and regulatory mechanisms involved in AMD. Additionally, it provides a useful resource for functional dissection of multiple other vision related traits.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×