Protective Effect of a Bispecific Fc-Fusion Protein on the Barrier of Human Retinal Pigment Epithelial Cells

Wang, J.; Wang, Yishen; Yu, Dechao; Liu, Qiuhui; Lin, Shaofen; Tian, Rong; Li, Jia; Luo, Yan

doi:10.1159/000515053

Cited by 2 publications

(2 citation statements)

References 34 publications

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“…Furthermore, it promotes the decay activity against C3 convertases [ 170 ]. Wang et al [ 171 ] claim that IBI302 could help to maintain the RPE integrity. A phase II study is now going (NCT04820452).…”

Section: Resultsmentioning

confidence: 99%

Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential

Stradiotto

Allegrini

Fossati

et al. 2022

IJMS

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Age-related macular degeneration (AMD) is a complex and multifactorial disease, resulting from the interaction of environmental and genetic factors. The continuous discovery of associations between genetic polymorphisms and AMD gives reason for the pivotal role attributed to the genetic component to its development. In that light, genetic tests and polygenic scores have been created to predict the risk of development and response to therapy. Still, none of them have yet been validated. Furthermore, there is no evidence from a clinical trial that the determination of the individual genetic structure can improve treatment outcomes. In this comprehensive review, we summarize the polymorphisms of the main pathogenetic ways involved in AMD development to identify which of them constitutes a potential therapeutic target. As complement overactivation plays a major role, the modulation of targeted complement proteins seems to be a promising therapeutic approach. Herein, we summarize the complement-modulating molecules now undergoing clinical trials, enlightening those in an advanced phase of trial. Gene therapy is a potential innovative one-time treatment, and its relevance is quickly evolving in the field of retinal diseases. We describe the state of the art of gene therapies now undergoing clinical trials both in the field of complement-suppressors and that of anti-VEGF.

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Section: Resultsmentioning

confidence: 99%

Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential

Stradiotto

Allegrini

Fossati

et al. 2022

IJMS

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“…Of note, RPE cells become more susceptible to complement-mediated damage ( 10 ). Complement and its receptor signaling may activate oxidative stress, contribute to transcriptional and metabolic homeostasis and promote inflammation in RPE ( 12 , 13 ). C3a and C5a, the bioactive fragments of C3 and C5, may upregulate the secretion of VEGF in RPE ( 14 ).…”

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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Protective Effect of a Bispecific Fc-Fusion Protein on the Barrier of Human Retinal Pigment Epithelial Cells

Cited by 2 publications

References 34 publications

Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential

Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential

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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