Reduced Expression of Synaptic Function and Neurotransmitter-Signaling Related Genes in Individuals with Neovascular AMD

Ellie Asadi and Dr.John Paul SanGiovanni, Department of Nutritional Sciences, University of Arizona, 1177 E 4th St, Tucson, Az 85721

Question and Purpose: We aim to determine whether sets of genes differentially expressed in neovascular-age-related macular degeneration (NV AMD) can be linked to the biological processes implicated in its pathophysiology.

Research Context. NV AMD is a great public health concern, as it is a leading cause of global blindness among elderly populations. Much of the work on the genetic basis of AMD has focused on DNA sequence variation analyzed from blood samples in genome-wide association studies; however, in our study, which is restricted to NV AMD only, all forms of advanced AMD transcriptomes were combined to derive the disease-associated differential expression profile.    

Methods. To understand the genetics of AMD, transcriptional profiles of the retina from control and NV AMD cases were generated using RNA-seq. We integrated retinal transcriptomes that covered 13,662 protein-coding and 1,462 noncoding genes and uploaded data files with normalized expression data matrices into the BioJupies website to generate the Jupyter notebook of functional annotations of our data. We focused on Gene Ontology (GO) enrichment analysis for our purposes.

Results. The top finding in GO Biological Processes is downregulated chemical synaptic transmission-related genes in NV AMD cases (p< 3.2 * 10^-16), and downregulated syntaxin-1 binding related genes (p< 3.2 * 10^ -8) in GO Molecular Function analysis. Work in our laboratory on human retinal pigment epithelial cells has implicated the L-DOPA and the DA system in the secretion of vascular endothelial growth factor, preceding retinal neovascularization. Fourteen DA-linked genes showed relatively lower expression in the retinas of NV AMD individuals (FDR = 0.00021, P-value = 4.4 *10 ^-6 ). 

Conclusions. Since our top findings across various databases belong to the central nervous system, we conclude that AMD could be linked to downregulated gene expressions in neurovascular systems or pathways related to regulating the delivery of neurotransmitters. 

Additional Abstract Information

Presenter: Ellie Asadi

Institution: University of Arizona

Type: Poster

Subject: Biology

Status: Approved

Time and Location

Session: Poster 2
Date/Time: Mon 3:00pm-4:00pm
Session Number: 2616