July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Identification of candidate gene and miRNA linked to early- and late-stage glaucoma
Author Affiliations & Notes
  • Lu Lu
    Department of Genetics, Genomics and Informatics, UTHSC, Memphis, Tennessee, United States
  • Michael Hook
    Department of Genetics, Genomics and Informatics, UTHSC, Memphis, Tennessee, United States
  • Fuyi Xu
    Department of Genetics, Genomics and Informatics, UTHSC, Memphis, Tennessee, United States
  • Siamak Yousefi
    Department of Genetics, Genomics and Informatics, UTHSC, Memphis, Tennessee, United States
    Department of Ophthalmology, UTHSC, Memphis, Tennessee, United States
  • Junming Yue
    Department of Pathology, UTHSC, Memphis, Tennessee, United States
  • Monica M Jablonski
    Department of Ophthalmology, UTHSC, Memphis, Tennessee, United States
  • Robert W Williams
    Department of Genetics, Genomics and Informatics, UTHSC, Memphis, Tennessee, United States
  • Footnotes
    Commercial Relationships   Lu Lu, None; Michael Hook, None; Fuyi Xu, None; Siamak Yousefi, None; Junming Yue, None; Monica Jablonski, None; Robert Williams, None
  • Footnotes
    Support  This study was supported by grant of Research to Prevent Blindness, and Mouse Strain Pilot Program of Center for Integrative and Translational Genomics (CITG) at UTHSC.
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1622. doi:
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    • Get Citation

      Lu Lu, Michael Hook, Fuyi Xu, Siamak Yousefi, Junming Yue, Monica M Jablonski, Robert W Williams; Identification of candidate gene and miRNA linked to early- and late-stage glaucoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1622.

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

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Abstract

Purpose : Molecular mediators of intraocular pressure (IOP) elevation and progression to blindness in glaucoma remain ill-defined, limiting the scope of early interventions and screening. Marked variability in rates of progression and severity of glaucomatous damage to retinal ganglion cells suggests that many factors are in play. Here we have analyzed the genetic modulation of glaucoma progression in a well-established murine model (DBA/2J), to better characterize molecular factors and their time course during disease.

Methods : Gene expression profiles of retinal tissue from DBA/2J (D2; n = 13) and control DBA/2J-Gpnmb+/+ (D2G; n = 12) mice (both sexes) were quantified and compared at different age cohorts (early stages 1–6 m and late stages 7–15 m) to identify differentially expressed genes (DEGs) between groups (DEG defined by p < 0.05 and fold-change > 1.3). Pooling was based on the well-documented timeframe for onset of glaucomatous damage in this strain. Additionally, we used previously gathered retina expression profiles of the BXD family of mice to construct a proposed microRNA (miRNA)-mediated molecular networks influencing glaucoma development using a systems genetics approach.

Results : 209 DEGs were identified with 143 in the early group (1–6 m), 66 in the late group (7–15 m) and 2 in both groups (Brp44l and Gpnmb). Early-group DEGs were primarily related to retinal structure and function, with top results comprised largely of crystallin heat shock family members. Late-group DEGs were primarily involved in innate immunity, including many members of the compliment cascade. Additionally, 3 miRNAs were identified that have significant negative correlation with Gpnmb expression, differential expression, and a fold change >1.5 (miR-125a-3p, miR-214-5p, miR-3076-5p).

Conclusions : Our results identified a number of differentially expressed genes between retinas of age-matched controls, early- and late stage glaucomatous retinas. We identified two well-known (miR-125a-3p and miR-214-5p), and one new (miR-3076-5p) miRNAs that appears to be linked to Gpnmb expression—a critical gene for glaucoma pathogenesis in this model.

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

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