June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
RNA-sequencing profile of Lenses of βA3ΔG91 Mice: A Model for Pediatric Congenital Nuclear Cataract
Author Affiliations & Notes
  • Akosua Konadu Boateng
    Optometry and Vision Science, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Roy Joseph
    Optometry and Vision Science, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Om P Srivastava
    Optometry and Vision Science, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Akosua Boateng, None; Roy Joseph, None; Om Srivastava, None
  • Footnotes
    Support  NIH Grant EY031303
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1507. doi:
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      Akosua Konadu Boateng, Roy Joseph, Om P Srivastava; RNA-sequencing profile of Lenses of βA3ΔG91 Mice: A Model for Pediatric Congenital Nuclear Cataract. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1507.

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

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Abstract

Purpose : Purpose: G91-deletion (ΔG91), a mutational hotspot in βA3-crystallin (CRYBA3/A1), causes pediatric congenital cataract in several families worldwide. However, the molecular mechanism of βA3ΔG91-induced cataract is presently unknown. The purpose of the study to understand the molecular mechanism through comparative analysis of gene expression profiles in lenses of βA3ΔG91- and wild-type mice.

Methods : Methods: We have generated βA3ΔG91 mouse model by the CRISPR-Cas9 methodology using the UAB Transgenic & Genetically Engineered Models Core (TGEMs) facility. Lenses from 1-month-old βA3ΔG91- and wild-type mice were examined for cataract development using Micron IV slit-lamp analysis. The relative protein profile by SDS-PAGE and the differential gene expression (transcriptome) followed by Ingenuity pathway analyses were performed in the 1-month old lenses of βA3ΔG91- and wild-type mice.

Results : Results: βA3ΔG91 mice showed congenital cataract relative to wild-type mice. SDS-PAGE analysis showed that βA3-crystallin level was relatively reduced in lenses of βA3ΔG91 mice compared to the wild-type mice, which seems to be due to its insolublization. The transcriptome analysis identified 93 dysregulated genes (q-value<0.05), out of which 11 genes were upregulated and 82 genes were downregulated. Biological function analysis revealed that the major affected genes were associated with protein synthesis, RNA damage and repair and cellular compromise. EIF2 signaling was identified as the top canonical pathway affected, showing that during congenital cataract development, ribosomal proteins (RPL, RPS) and genes involved in cellular stress (GADD34) were downregulated.

Conclusions : Conclusions: Our study provides informative data about the potentially affected candidate genes and biological mechanisms during βA3ΔG91-induced congenital cataract development. Taken together, targeting EIF2 signaling might be a stepping-stone in developing therapeutic strategies to mitigate the congenital cataract.

This is a 2021 ARVO Annual Meeting abstract.

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