June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Differential Expression Patterns of Genes Encoding Monoamine Pathway Constituents Exist in Retinal Specimens of People with Neovascular AMD
Author Affiliations & Notes
  • John Paul SanGiovanni
    BIO5 Institute, University of Arizona, Tucson, Arizona, United States
  • Daniel Quentin SanGiovanni
    Emory University, Atlanta, Georgia, United States
  • Robert W Snyder
    Biomedical Engineering, University of Arizona, Tucson, Arizona, United States
  • Dawn L Geiser
    Nutritional Sciences, University of Arizona, Tucson, Arizona, United States
  • Brian S McKay
    Ophthalmology and Vision Science, University of Arizona, Tucson, Arizona, United States
  • Footnotes
    Commercial Relationships   John Paul SanGiovanni, None; Daniel SanGiovanni, None; Robert Snyder, Snyder Biomedical (I), Snyder Biomedical (E), Snyder Biomedical (WO/2020/160256) (P); Dawn Geiser, None; Brian McKay, Snyder Biomedical (P)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1509. doi:
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      John Paul SanGiovanni, Daniel Quentin SanGiovanni, Robert W Snyder, Dawn L Geiser, Brian S McKay; Differential Expression Patterns of Genes Encoding Monoamine Pathway Constituents Exist in Retinal Specimens of People with Neovascular AMD. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1509.

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

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Abstract

Purpose : We have previously applied methods in genomics, structural chemistry, ophthalmic epidemiology and clinical trials to demonstrate associations of L-DOPA, dopamine (DA) and monoaminergic receptors with advanced AMD. In this work we report findings on human retinal transcriptomes to extend our investigations.

Methods : We used QC-validated and normalized RNA-seq data collected with Illumina HiSeq 2500 from a public-access NCBI GEO database (GSE115828) of retinal specimens in order to identify differential gene expression profiles in seven people with neovascular AMD (NV AMD), relative to twelve age-matched AMD-free peers. We conducted gene ontology and pathway analysis with Gene Set Enrichment Analysis (GSEA) software.

Results : RNA levels of DBH-like monooxygenase protein 1 (MOXD1), an enzyme implicated in dopamine catabolism, were 3.3-fold higher in retinal specimens of people with NV AMD (P < 9.91E-5; FDR Q = 0.095) – these findings were concordant with a published work reporting a 2.8-fold increase in MOXD1 expression within macular specimens of people with NV AMD (PMID: 22364233). Gene Ontology Enrichment Analysis on the full set of 17910 transcripts yielded strongest relationships for down regulation of chemical synaptic transmission (GO: 0007268; FDR Q = 6.3E-13) in the NV AMD cohort – subsequent Pathway Enrichment Analysis showed significant NV AMD-associated retinal down regulation of 14 genes in the KEGG Dopamine Synapse Pathway (hsa04728; FDR Q = 1.4E-4) and 4 genes in the WikiPathways Nicotine Effect on Dopaminergic Neurons Pathway (WP1602; FDR = 0.048). Gene sets from the Reactome Dopamine Release Cycle (FDR Q = 0.14) and Gene Ontology Regulation of Dopamine Secretion (FDR Q = 0.17) also showed significantly lower experession values in people with NV AMD.

Conclusions : Our findings strengthen inferences on AMD-associated alterations in function of monoaminergic signaling pathways.

This is a 2021 ARVO Annual Meeting abstract.

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