The Complement System in Retinal Detachment with Choroidal Detachment

Luo, Shasha; Chen, Yanghao; Yang, Lufei; Gong, Xuechun; Wu, Zhifeng

doi:10.1080/02713683.2022.2038634

Cited by 4 publications

(3 citation statements)

References 24 publications

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“…Although the exact role of complement and coagulation cascades in DR remains unclear, some studies have suggested that there is dysregulation and activation of the alternative pathway ( 76 , 77 ). Likewise, the activation of the complement was reported in RD/PVR ( 44 , 45 , 52 , 78 , 79 ), as well as its involvement in pathological processes, such as increased vascular permeability, endothelial cell proliferation, migration, RPE atrophy, reactive gliosis, and loss of photoreceptor outer segments ( 45 , 66 ). On the other hand, genetic studies strongly support the association between complement components (e.g., CO3, CFH, and CFB) and the risk for AMD ( 80 – 82 ).…”

Section: Discussionmentioning

confidence: 86%

Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases

et al. 2023

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IntroductionDiabetic retinopathy (DR) and age-related macular degeneration (AMD) are leading causes of visual impairment and blindness in people aged 50 years or older in middle-income and industrialized countries. Anti-VEGF therapies have improved the management of neovascular AMD (nAMD) and proliferative DR (PDR), no treatment options exist for the highly prevalent dry form of AMD.MethodsTo unravel the biological processes underlying these pathologies and to find new potential biomarkers, a label-free quantitative (LFQ) method was applied to analyze the vitreous proteome in PDR (n=4), AMD (n=4) compared to idiopathic epiretinal membranes (ERM) (n=4). Results and discussionPost-hoc tests revealed 96 proteins capable of differentiating among the different groups, whereas 118 proteins were found differentially regulated in PDR compared to ERM and 95 proteins in PDR compared to dry AMD. Pathway analysis indicates that mediators of complement, coagulation cascades and acute phase responses are enriched in PDR vitreous, whilst proteins highly correlated to the extracellular matrix (ECM) organization, platelet degranulation, lysosomal degradation, cell adhesion, and central nervous system development were found underexpressed. According to these results, 35 proteins were selected and monitored by MRM (multiple reaction monitoring) in a larger cohort of patients with ERM (n=21), DR/PDR (n=20), AMD (n=11), and retinal detachment (n=13). Of these, 26 proteins could differentiate between these vitreoretinal diseases. Based on Partial least squares discriminant and multivariate exploratory receiver operating characteristic (ROC) analyses, a panel of 15 discriminatory biomarkers was defined, which includes complement and coagulation components (complement C2 and prothrombin), acute-phase mediators (alpha-1-antichymotrypsin), adhesion molecules (e.g., myocilin, galectin-3-binding protein), ECM components (opticin), and neurodegeneration biomarkers (beta-amyloid, amyloid-like protein 2).

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Section: Discussionmentioning

confidence: 86%

Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases

et al. 2023

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“…This study showed that the incidence of ERM was significantly increased in patients with choroidal detachment, which may result from blood-retinal barrier destruction and excessive inflammatory response. Accumulating evidence from recent experimental and clinical studies on the identification of inflammatory mediators in the vitreous show that RRDCD is associated with higher expressions of plasma proteins, proinflammation cytokines, chemokines, immunoglobulin chains, and complement proteins than RRD [19][20] . These factors may aggravate inflammation, facilitate the proliferation and differentiation of RPE, mediate lymphocyte migration, and facilitate the accumulation of the extracellular matrix [21] .…”

Section: Resultsmentioning

confidence: 99%

Predictive factors of epiretinal membrane in complicated rhegmatogenous retinal detachment tamponaded with silicone oil

Qian,

Sun,

Mijit

et al. 2023

Int J Ophthalmol

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AIM: To determine the incidence and predictive factors for epiretinal membrane (ERM) formation in eyes with complicated primary rhegmatogenous retinal detachment (RRD) tamponaded with silicone oil (SO). METHODS: This retrospective case-control study included 141 consecutive patients with (51 eyes) and without (90 eyes) ERM formation after primary pars plana vitrectomy (PPV) and SO tamponade for complicated RRD. The risk factors for ERM were assessed using logistic regression analysis. RESULTS: The prevalence of postoperative ERM was 36.2% (51/141). Multivariate logistic regression analysis showed that the risk factors for ERM in SO-tamponaded eyes included preoperative proliferative vitreoretinopathy [PVR; odds ratio (OR), 2.578; 95% confidence interval (CI) 1.580–4.205, P<0.001], preoperative choroidal detachment (OR, 4.454; 95%CI 1.369–14.498, P=0.013), and photocoagulation energy (OR, 2.700; 95%CI 1.047–6.962, P=0.040). The duration of the preoperative symptoms, intraocular SO tamponade time, giant retinal tear, preoperative vitreous hemorrhage, preoperative best-corrected visual acuity, number of breaks, quadrants of RRD, axial length, and photocoagulation points were not predictive factors for ERM formation. CONCLUSION: Preoperative PVR, choroidal detachment, and photocoagulation energy are risk factors of ERM formation after complicated RRD repair. Better ophthalmic care as well as patient education are necessary for such patients with risk factors.

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“…Growing evidence has revealed the vital role of complement signaling in retinal physiopathology ( 9 , 10 ). Complement components, such as C2, C4b, C5/C5a and C9, have been indicated to be elevated in the vitreous humor of patients with RRDCD ( 11 ). Of note, RPE cells become more susceptible to complement-mediated damage ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

The complement C3a‑C3aR and C5a‑C5aR pathways promote viability and inflammation of human retinal pigment epithelium cells by targeting NF‑κB signaling

Luo

Gong

et al. 2022

Exp Ther Med

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Retinal detachment (RD) and its special form of rhegmatogenous RD associated with choroidal detachment (RRDCD) feature similar pathological alterations, including enhanced retinal cell inflammation. Although the importance of the complement components C3a and C5a and their corresponding receptors in retinal maintenance has been demonstrated, the relevance of these molecules to the pathogenesis of RD or RRDCD remains to be investigated. The contents of C3a, C5a and inflammatory factors, such as TNF-α, IL-1β, IL-6 and prostaglandin (PG)E2, in related clinical samples were examined by ELISA. Subsequently, human retinal pigment epithelial (HRPE) cells were subjected to challenge with the C3a and C5a recombinant proteins with or without C3a and C5a antagonists and NF-κB inhibitor, and the cell viability and inflammatory cytokines were then determined by a Cell Counting Kit-8 assay and ELISA, respectively. In addition, reverse transcription-quantitative PCR and western blot analyses were utilized to examine the mRNA or/and protein levels of C3a and its receptor C3aR, as well as C5a and its receptor C5aR, and NF-κB. In addition, the correlation of C3a and C5a with the aforementioned inflammatory factors was analyzed. The inflammatory factor levels of C3a and C5a were considerably elevated in patients with RRDCD compared to those in the controls. Consistently, C3a and C5a treatment led to increased cell viability and aggravated inflammation in HRPE cells. Accordingly, C3a and C5a induced upregulation of their corresponding receptors C3aR and C5aR, which was in turn observed to be linked to the activation of the NF-κB signaling pathway. Furthermore, there was a positive correlation of the complements C3a and C5a with individual TNF-α, IL-1β, IL-6 and PGE2. Taken together, the C3a-C3aR and C5a-C5aR pathways were indicated to promote cell viability and inflammation of HRPE cells by targeting the NF-κB signaling pathway.

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The Complement System in Retinal Detachment with Choroidal Detachment

Cited by 4 publications

References 24 publications

Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases

Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases

Predictive factors of epiretinal membrane in complicated rhegmatogenous retinal detachment tamponaded with silicone oil

The complement C3a‑C3aR and C5a‑C5aR pathways promote viability and inflammation of human retinal pigment epithelium cells by targeting NF‑κB signaling

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