June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Transcriptome Analysis of ALDH3A1-null Mice Elucidates New Roles of Corneal Crystallins
Author Affiliations & Notes
  • Nicholas Apostolopoulos
    Department of Ophthalmology & Visual Science, Yale School of Medicine, New Haven, Connecticut, United States
  • Ying Chen
    Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, United States
  • Xiaoqing Yu
    Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, United States
  • Hongyu Zhao
    Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, United States
  • David Thompson
    Department of Clinical Pharmacology, University of Colorado School of Pharmacy, Denver, Colorado, United States
  • Vasilis Vasiliou
    Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, United States
    Department of Ophthalmology & Visual Science, Yale School of Medicine, New Haven, Connecticut, United States
  • Footnotes
    Commercial Relationships   Nicholas Apostolopoulos, None; Ying Chen, None; Xiaoqing Yu, None; Hongyu Zhao, None; David Thompson, None; Vasilis Vasiliou, None
  • Footnotes
    Support  NIH grants EY021688
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1400. doi:
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      Nicholas Apostolopoulos, Ying Chen, Xiaoqing Yu, Hongyu Zhao, David Thompson, Vasilis Vasiliou; Transcriptome Analysis of ALDH3A1-null Mice Elucidates New Roles of Corneal Crystallins. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1400.

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

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Abstract

Purpose : ALDH3A1 is a corneal crystallin that causes a profound retardation in cell proliferation, decreased light scattering in vitro and protection against oxidative stress. Corneal injury decreases ALDH3A1 and triggers cell proliferation and the development of corneal haze due to increase light scattering. Our congenic Aldh3a1 knockout (KO) mice exhibit corneal haze. The aim of the current study was to quantify transcriptome changes associated with the ALDH3A1-mediated corneal haze using RNA-seq analysis of corneas from KO and wild type (WT) mice.

Methods : RNA-seq analysis was performed in twelve week old WT and KO mice (N=4 per genotype). Differentially expressed genes in KO mice were identified as those with a minimum fold-change of +/− 2 and a Benjamini-Hochberg corrected p-value ≤0.05 relative to WT mice. MetaCore™ was used for pathway analyses and real time-quantitative PCR (qPCR) was used to confirm candidate genes. Student’s unpaired t-test was used to delineate significant differences (p < 0.05).

Results : RNA-seq analyses revealed approximately 300 upregulated and 200 downregulated genes in KO corneas (p < 0.05). Pathway analyses revealed apoptosis, transcription regulation, and cell cycle regulation as the most highly upregulated pathways, whereas synaptogenesis, IL13-mediated immune response, and O-glycan biosynthesis were the most highly downregulated pathways.

Conclusions : Our results extend our previous studies in demonstrating that ALDH3A1 may modulate corneal transparency by regulating cell cycle and apoptosis. In addition, by influencing synaptogenesis, the IL13-mediated immune response, and O-glycan synthesis, alterations in ALDH3A1 may also be involved in dry eye disease, ocular allergic responses, and corneal susceptibility to bacterial/parasitic infections. Metabolomic, lipidomic and proteomic analyses are underway to further define the role of ALDH3A1 in these conditions.

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

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