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

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-1ß, 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-1ß, 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.

Internal limiting membrane packing for treatment of morning glory syndrome with rhegmatogenous retinal detachment.

Purpose: This study aimed to report the ocular features, surgical methods, and surgical outcomes of a patient with morning glory syndrome(MGS) complicated with rhegmatogenous retinal detachment(RRD). Observations: The patient was a 38-year-old Chinese woman with congenital cataract in her left eye and an artificial eye in her right eye. Ocular examination confirmed MGS complicated with RD in the left eye and revealed a retinal hole in the temporal margin of the optic disc. The retina successfully reattached after pars plana vitrectomy(PPV), silicone oil tamponade and laser photocoagulation, but the hole did not close and occurred obvious contractile movement. The retina did not detach again during the follow-up period. One and a half years later, silicone oil removal combined with internal limiting membrane and hyaloid or glial remnant plugging, autologous blood covering and C3F8 filling were performed, and the retinal hole was finally closed. Conclusions and importance: This case is the first to report contractile movement of the retinal hole in a patient with MGS complicated with RD, and the hole was closed by internal limiting membrane tamponade combined with autologous blood coverage.

Quantitative proteomics analysis of human vitreous in rhegmatogenous retinal detachment associated with choroidal detachment by data-independent acquisition mass spectrometry.

The prognosis of rhegmatogenous retinal detachment (RRD) with choroidal detachment (RRDCD) is often poor and complicated. This study focused on the identification of the characteristic proteins and signal pathways associated with the etiology of RRDCD and to provide guidance for diagnosis and treatment of RRDCD. In this study, vitreous humor samples were obtained from 16 RRDCD patients, 14 with RRD, 12 with idiopathic epiretinal macular membrane (IEMM), and 5 healthy controls from donated corpse eyes. Data-independent acquisition mass spectrometry and bioinformatics analysis were employed to identify differentially expressed proteins (DEPs). In the vitreous humor, 14,842 peptides were identified. Patients with RRDCD had 249 DEPs (93 upregulated and 156 downregulated), with 89 in patients with RRD and 61 in patients with IEMM. Enrichment analysis of the GO and Kyoto Encyclopedia of Genes and Genomes DEP databases indicated functional clusters related to inflammation and immunity, protein degradation and absorption, cell adhesion molecules (CAMs), the hedgehog signaling pathway, and lipid metabolism. Weighted gene co-expression network analysis showed that DEPs with positive co-expression of RRDCD participated in immune-related pathways led by the complement and coagulation cascade, whereas DEPs with negative co-expression of RRDCD participated in protein degradation and absorption, CAMs, and the hedgehog signaling pathway. In summary, our study provides important clues and the theoretical basis for exploring the pathogenesis, progression, and prognosis of ocular fundus disease.

The Complement System in Retinal Detachment with Choroidal Detachment.

PURPOSE: This study aims to explore the differences in the levels of complement components and complement regulatory factors in the vitreous humor of patients with retinal detachment with choroidal detachment (RRDCD), patients with rhegmatogenous retinal detachment (RRD). METHODS: A prospective case-control study design was used to recruit 20 patients with RRDCD and 20 patients with RRD in consecutive cases who underwent pars plana vitrectomy from March 2019 to January 2020. The control group comprised 15 patients with epiretinal membrane and 5 eyes from cadavers. The concentrations of complement C2, complement C4b, complement C5/C5a, complement C9, complement factor D (CFD), lectin, and complement factor I (CFI) were measured using Multiplex Luminex Assay, and the concentration of soluble decay acceleration factor (sDAF) was measured using ELISA. RESULTS: As compared with the RRD and control groups, complement C2, complement C4b, complement C5/C5a, complement C9, CFD, lectin, CFI, and sDAF were significantly increased in the RRDCD group. Additionally, as compared with the control group, the concentrations of complement component C2 and CFD were significantly increased in the vitreous humor of the RRD group. CONCLUSION: Components of all three complement pathways were elevated in eyes with RRDCD. Interestingly, while there was evidence of early complement activation in RRD, the final common pathway components were not elevated. In contrast, RRDCD eyes showed significant elevations of the MAC complex components, underscoring a potential pathophysiologic impact of complement activation in this condition.