Abstract
Purpose :
Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in those older than 50. There is no diagnostic test for NAION, although there is evidence of post-ischemic inflammation in NAION,. In this study, we performed a comprehensive cytokine profiling of plasma from NAION patients and mouse model compared with controls.
Methods :
We collected blood from 28 human subjects (18 NAION (4 acute, 14 chronic; 2 serial data), 10 controls) and 10 adult C57BL/6 mice (5 with unilateral NAION induced by photochemical thrombosis one day prior, 5 controls). NAION was confirmed by clinical exam and optical coherence tomography (OCT). Plasma analyzed using 76-plex (human) or 39-plex (mice) cytokine arrays (Luminex). We used cultured human retinal endothelial cells to assess biological activity of 3 human NAION plasma compared with controls.
Results :
Comprehensive plasma profiling revealed dramatic changes in cytokine profiles in human and mouse model of NAION compared with controls, consistent with increased inflammation. In human NAION, 21 cytokines increased >1.5x above control levels, and none decreased to <0.5x. In mouse NAION, 4 cytokines increased >1.5x, and 2 cytokines decreased to 0.5x. In both human and mouse NAION, the most upregulated cytokines were C-C motif chemokine CCL11, the the protein most correlated with human aging (Villeda et al, 2011, Nature), and monocyte-chemoattractant protein MCP3. In human chronic NAION, CCL11 was also increased, and cytokines that increased the most was CXCL5, CXCL13 and IL1a. Most dramatic increases of these cytokines were observed in bilateral NAION. Plasma from 3 human NAION patients had biological activity on cultured human retinal endothelial cells, by increasing angiogenesis and disrupting endothelial barrier.
Conclusions :
There is evidence of increased inflammation in both acute and chronic human NAION and in mouse model of acute NAION, with prominent increase in several plasma cytokines, including CCL11, MCP3 and CXCL5. The most upregulated cytokine in both human and animal acute NAION was CCL11. Larger prospective studies are needed to understand the relation of NAION and inflammation, including on the risk of second eye involvement, These cytokines or their receptors are potential candidates for biomarkers and therapeutic targets in NAION.
This is a 2020 ARVO Annual Meeting abstract.