IL-18 and S100A12 Are Upregulated in Experimental Central Retinal Vein Occlusion

Abstract

Retinal vein occlusion (RVO) is a common retinal vascular disease. RVO may be complicated by pronounced ischemia that often leads to severe loss of visual function. The present work aimed at studying the retinal proteome of RVO complicated by ischemia. In six Danish Landrace pigs RVO was induced with argon laser in the right eye of each animal. As four retinal veins were occluded, the RVO best corresponded to a central retinal vein occlusion (CRVO). Left control eyes received a similar laser treatment without inducing occlusion. RVO and retinal ischemia were verified by angiography. The retinas were collected 15 days after RVO for proteomic analysis. RVO resulted in a downregulation of proteins involved in visual perception, including rhodopsin, transducin alpha chain, and peripherin-2. RVO also caused a downregulation of proteins involved in neurotransmitter transport, including glutamate decarboxylase 1 (GAD1), glutamate decarboxylase 2 (GAD2), and complexins 2–4. RVO lead to increased contents of proteins involved in inflammation, including interleukin-18 (IL-18), S100A12, and annexin A1 (ANXA1). Immunohistochemistry revealed a general retinal upregulation of IL-18 and ANXA1 while S100A12 was highly abundant in retinal ganglion cells in RVO. IL-18 and S100A12 are likely to be driving forces in the inflammatory response of RVO complicated by ischemia. Our findings also suggest that RVO results in compromised neurotransmission and a downregulation of proteins involved in visual perception.

Aqueous Fibronectin Correlates With Severity of Macular Edema and Visual Acuity in Patients With Branch Retinal Vein Occlusion: A Proteome Study

“…S100A7, S100A8, and S100A9 belong to the S100 protein family of small calcium-binding proteins 42 that contribute to lipopolysaccharide response in a TLR4 dependent manner. 42 We have previously suggested that proteins of the S100 family are regulated in retinal vein occlusion 22 and our study indicates that the turnover of S100 proteins is altered in BRVO. However, the S100 proteins did not correlate with CRT and BCVA, and our data does not provide an underlying explanation for the S100 regulation.…”

“…Mass spectrometry data were further processed with Perseus software version 1.6.2.3 (Max Planck Institute of Biochemistry, Martinsried, Germany; https://maxquant.net/perseus/ ) to remove poorly identified proteins as described in a previous article. 22 LFQ values were log 2 transformed, and mean LFQ values were calculated. At least two unique peptides were required for successful protein identification.…”

Rhodopsin: A Potential Biomarker for Neurodegenerative Diseases

“…Coincidentally, individuals with RVO are also at a significantly greater risk of developing ischemic and hemorrhagic strokes (Chen et al, 2018). In one study, RVO was induced in pigs, which led to a reduction in proteins involved in vision, such as rhodopsin (Cehofski et al, 2018). This compromise in rhodopsin function suggests that neurotransmission is sensitive to ischemic insult.…”

Aflibercept Intervention in Experimental Branch Retinal Vein Occlusion Results in Upregulation of DnaJ Homolog Subfamily C Member 17

“…Animals were housed under a 12 h light/dark cycle. Anesthesia, topical anesthesia with eye drops, and dilation of the pupils were performed as previously described [ 22 ].…”

“…Mass spectrometry data was processed further with Perseus software version 1.6.2.3 [ 28 ] to remove poorly identified proteins as described in a previous article [ 22 ]. LFQ values were log2-transformed.…”