Changes in complement activation products after anti-VEGF injection for choroidal neovascularization in age-related macular degeneration and pachychoroid disease

Tanaka, Keiichiro; Oguchi, Yasuharu; Omori, Tomoko; Ishida, Yumi; Shintake, Hiroaki; Tomita, Ryutaro; Kasai, Akihito; Ogasawara, M.; Sugano, Yukinori; Itagaki, Kanako; Ojima, Akira; Machida, Takeshi; Sekine, Hideharu; Sekiryu, Tetsuju

doi:10.1038/s41598-021-87340-6

Cited by 10 publications

(10 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, RGS1 promotes melanoma progression by phosphorylation of protein kinase B and extracellular signal-regulated protein kinase ( 8 ). Dysregulation of the complement system can be induced after anti-VEGF therapy, and induce the C3a, C4a increase in AMD ( 39 ). The increased secretion of complement promotes the activation of inflammatory cells.…”

Section: Discussionmentioning

confidence: 99%

Regulator of G-protein signaling 1 promotes choroidal neovascularization in age-related macular degeneration

Zhang¹,

Zhang²,

Guo³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

Background: Age-related macular degeneration (AMD) is the leading cause of blindness, and is associated with oxidative stress and the development of new blood vessels. At present, the main clinical treatment for AMD includes intraocular injection of vascular endothelial growth factor (VEGF). However, treatment includes repeated injections with significant side-effects. Therefore, new treatment options are required. The aim of the present study was to discover the new treatment target of AMD from the gene level. Methods: The Gene Expression Omnibus (GEO) database was used to analyze the differential gene expression in AMD, and the regulator of G-protein signaling 1 (RGS1) was obtained by bioassay. Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression levels of RGS1, VEGF, and other related molecules in human microvascular endothelial cells (HMECs) under different conditions. Cell viability, apoptosis, and proliferation of HMECs were measured by Cell Counting Kit-8 proliferation assay. Immunofluorescence and immunohistochemistry detected the interaction between RGS1, platelet endothelial cell adhesion molecule-1, and VEGF. Results: RGS1 was found to closely associated with the proliferation of vascular endothelial cells, and therefore, with angiogenesis. The expression of RGS1, VEGF, and platelet endothelial cell adhesion molecule-1 was upregulated in laser model mice and hypoxia model HMECs. Knockout of RGS1 inhibits the expression of VEGF and HMEC proliferation, thereby inhibiting AMD angiogenesis. Conclusions: Our results support the use of RGS1 as a new potential target for the future treatment of AMD.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulator of G-protein signaling 1 promotes choroidal neovascularization in age-related macular degeneration

Zhang¹,

Zhang²,

Guo³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…The reported prevalence of polypoidal lesions was 48–56% ( Table 7 ) [ 60 , 61 , 62 , 63 ]. However, several other studies from Japan have performed their analysis, limiting their study target only to PNV without polypoidal lesions [ 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. Among these studies, one study considered that PNV included both PNV with and those without polypoidal lesions, and they performed their analysis only on PNV without polypoidal lesions [ 64 ].…”

Section: Establishment Of the Pachychoroid Conceptmentioning

confidence: 99%

“…Among these studies, one study considered that PNV included both PNV with and those without polypoidal lesions, and they performed their analysis only on PNV without polypoidal lesions [ 64 ]. Other studies considered PNV without polypoidal lesions as PNV, and PNV with polypoidal lesions as PCV [ 67 , 68 , 69 , 70 , 71 ]. In 2019, a study from South Korea compared anti-VEGF treatment outcomes for PNV and nAMD after excluding eyes with polypoidal lesions [ 72 ].…”

Section: Establishment Of the Pachychoroid Conceptmentioning

confidence: 99%

Relationship between Pachychoroid and Polypoidal Choroidal Vasculopathy

Yamashiro

Yanagi

Koizumi

et al. 2022

JCM

View full text Add to dashboard Cite

Previous clinical studies have suggested that pachychoroid can induce macular neovascularization (MNV) to develop pachychoroid neovasculopathy (PNV) and that PNV can progress to polypoidal choroidal vasculopathy (PCV). Recent studies based on the pachychoroid concept are now gradually revealing the true nature of, at least some part of, PCV. However, previous studies on PNV and/or PCV have used different frameworks for the classification of PNV, PCV, and neovascular age-related macular degeneration (nAMD). These have hampered the rapid overhaul of the understanding of PCV. Some investigators have assumed that all PCV is pachychoroid-driven whereas other investigators have classified PCV into “pachychoroid PCV” and “non-pachychoroid PCV”. Furthermore, since there is no consensus as to whether PNV includes PCV, some studies have included PCV with PNV, while other studies have excluded PCV from PNV. To address these gaps, we summarize previous studies on PCV and pachychoroid. Even before the proposal of the pachychoroid concept, previous studies had suggested that PCV could be divided into two subtypes, of which one was characterized by pachychoroid features. Previous studies had also provided keys to understand relationship between PCV and PNV. We here recommend a refined conceptual framework for future studies on PNV, PCV, and nAMD. Considering the current inconsistent understanding of PCV, we should be cautious about using the term PCV until we understand the true nature of PCV.

show abstract

“…It can be cautiously assumed that the possible reasons for irregular MNV activity in nAMD are associated with the immune processes in the choroid. Moreover, recent study demonstrated dysregulation of the complement system following anti-VEGF therapy for nAMD [ 44 ]. The authors concluded that the interaction between anti-VEGF therapy and the complement system may be associated with ocular tissue damage after anti-VEGF treatment, affecting the clinical outcomes of anti-VEGF therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Regardless of whether it is pathogenic or not, VEGF production may return at some period. Nevertheless, prolonged unnecessary complement activation by anti-VEGF therapy might diminish the effectiveness of anti-VEGF injections or cause tissue injury due to local VEGF depletion [ 44 ]. In such cases, when determining a treatment regimen for patients with risk alleles in complement-associated genes, especially regulatory proteins (FI and FH), overtreatment should be taken into account to minimize the negative effects of anti-VEGF therapy.…”

Section: Discussionmentioning

confidence: 99%

Association between Polymorphisms in CFH, ARMS2, CFI, and C3 Genes and Response to Anti-VEGF Treatment in Neovascular Age-Related Macular Degeneration

et al. 2022

View full text Add to dashboard Cite

Neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly. The gold standard of nAMD treatment is intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors. Genetic factors may influence the response to anti-VEGF therapy and result in a high degree of response variability. The aim of the study was to evaluate the association of the polymorphisms in genes related to the complement system (rs2285714-CFI, rs10490924-ARMS2, rs2230199-C3, rs800292-CFH, and rs6677604-CFH) with nAMD its clinical features and optical coherent tomography (OCT) biomarkers of treatment response to anti-VEGF therapy. Genotyping by allele-specific PCR was performed in 193 AMD patients and 147 age-matched controls. A prospective study of the dynamics of changes in OCT biomarkers during aflibercept treatment included 110 treatment-naive patients. Allele T rs10490924 was associated with the increased risk of nAMD. For both rs800292 and rs6677604, carriage of the A allele was protective and decreased the nAMD risk. Associations of rs2230199 with central retinal thickness (CRT) and intraretinal cysts were revealed. The height of pigment epithelium detachment and the height of neuroretinal detachment were significantly higher in carriers of the minor allele of rs2285714, both at baseline and during treatment. The reduction of CRT was associated with higher CRT at baseline and the presence of the T allele of rs2285714. By the end of one-year follow-up the patients homozygous for the minor allele rs2285714 had significantly higher odds of the presence of anastomoses and loops and active neovascular membrane. Furthermore, minor allele carriers had decreased levels of complement factor I level in aqueous humor but not in the plasma, which may be due to the influence of rs2285714 on tissue-specific splicing. Our results suggest that the severity of AMD macular lesions is associated with rs2285714 and rs2230199 polymorphisms, which could be explained by their high regulatory potential. Patients with the minor allele of rs2285714 respond worse to antiangiogenic therapy.

show abstract

Changes in complement activation products after anti-VEGF injection for choroidal neovascularization in age-related macular degeneration and pachychoroid disease

Cited by 10 publications

References 39 publications

Regulator of G-protein signaling 1 promotes choroidal neovascularization in age-related macular degeneration

Regulator of G-protein signaling 1 promotes choroidal neovascularization in age-related macular degeneration

Relationship between Pachychoroid and Polypoidal Choroidal Vasculopathy

Association between Polymorphisms in CFH, ARMS2, CFI, and C3 Genes and Response to Anti-VEGF Treatment in Neovascular Age-Related Macular Degeneration

Contact Info

Product

Resources

About