Abstract
Purpose :
Anterior ischemic optic neuropathy (NAION) continues to be the most common acute optic neuropathy in older adults. Unlike its typical presentation, NAION in younger patients is associated with optic disc drusen (ODD-AION) with less cardiovascular (CVS) risk factors. Despite their clinical significance, our understanding of the underlying molecular mechanisms remains limited. Hence, we aimed to compare key proteins involved in NAION and ODD-AION through a cross-sectional proteomics analysis.
Methods :
Three patient groups were recruited: ODD-AION patients (n=3), NAION patients (n=5), and age-matched controls (n=3). We isolated skin fibroblasts from the three groups and performed proteomics analysis to identify differentially expressed proteins (DEP) associated with NAION and ODD-AION. Differential expression of proteins was determined based on -log10 p-values calculated using a two-sample t-test. Cluster analysis for Gene ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG) pathways, and protein-protein interaction was performed on the DEP using DAVID bioinformatics and STRING tools.
Results :
A total of 7562 proteins were identified in the samples. 266 and 213 DEP were significantly changed in the ODD-AION and NAION patients, respectively (p<0.05). Among these, 29 overlapped in the two groups. Cluster analysis of the 237 unique ODD-AION DEP demonstrated the highest protein-protein interaction in vesicle transport and membrane fusion of endosomes and lysosomes, particularly in protein complex structure and protein binding (p<0.05). In comparison, the 184 unique NAION DEP were mainly enriched in ribosomal biogenesis and rRNA processing, particularly in ribosomal structure and RNA binding (p<0.05). The up-regulated NAION DEP were distinctly involved in carbohydrate metabolism and glycogen storage disease. Tissue expression of the ODD-AION DEP was higher in the blood/plasma, whereas it was higher in the CVS for NAION DEP.
Conclusions :
This analysis provided an insight on the biological functions and pathways involved in the NAION and ODD-AION disease processes as well as potential biomarkers. Despite clinical similarities, they showed differences at a molecular level. ODD-AION involved changes in the protein degradation process while NAION proteins were related to the ribosomal function. Carbohydrate metabolism involvement and CVS tissue expression may explain the CVS risk factors association with NAION.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.