HTRA1 and TGF-β1 Concentrations in the Aqueous Humor of Patients With Neovascular Age-Related Macular Degeneration

Tosi, Gian Marco; Caldi, Elena; Neri, Giovanni; Nuti, Elisabetta; Marigliani, Davide; Baiocchi, Stefano; Traversi, Claudio; Cevenini, Gabriele; Tarantello, Antonio; Fusco, Fiorella; Nardi, Federica; Orlandini, Maurizio; Galvagni, Federico

doi:10.1167/iovs.16-20922

Cited by 49 publications

(38 citation statements)

References 30 publications

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“…A study of the mice model of arthritis also showed the increase in HtrA1 expression (Hou et al, 2013). Furthermore, HtrA1 is implicated in Age-related macular degeneration (AMD) (Horie-Inou & Inou, 2014;Tosi et al, 2017) and it is now widely accepted that inflammation and the immune system plays important roles in AMD pathogenesis (Iannaccone et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Immune response against HtrA proteases in children with cutaneous mastocytosis

Renke

Kędzierska‐Mieszkowska

Lange

et al. 2018

Acta Biochim Pol

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Mast cells play an important role in both, the innate and adaptive immunity, however, clonal proliferation of abnormal mast cells in various organs leads to mastocytosis. A skin variant of the disease, cutaneous mastocytosis (CM) is the most frequent form of mastocytosis in children. HtrA proteases are modulators of important cellular processes, including cell signaling and apoptosis, and are related to development of several pathologies. The above and the observation that mast cells constitutively release the HtrA1 protein, prompted us to investigate a possible involvement of the HtrA proteins in pediatric CM. Levels of the serum autoantibodies (IgG) against the recombinant HtrA proteins (HtrA1-4) in children with CM (n=36) and in healthy controls (n=62) were assayed. Anti-HtrA IgGs were detected using enzyme linked immunosorbent assay (ELISA) and Western-blotting. In the CM sera, levels of the anti-HtrA1 and anti-HtrA3 autoantibodies were significantly increased when compared to the control group, while the HtrA protein levels were comparable. No significant differences in the anti-HtrA2 IgG level were found; for the anti-HtrA4 IgGs lower levels in CM group were revealed. In healthy children, the IgG levels against the HtrA1, -3 and -4 increased significantly with the age of children; no significant changes were observed for the anti-HtrA2 IgG. Our results suggest involvement of the HtrA1 and HtrA3 proteins in pediatric CM; involvement of the HtrA4 protein is possible but needs to be investigated further. In healthy children, the autoantibody levels against HtrA1, -3 and -4, but not against HtrA2, increase with age.

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Section: Discussionmentioning

confidence: 99%

Immune response against HtrA proteases in children with cutaneous mastocytosis

Renke

Kędzierska‐Mieszkowska

Lange

et al. 2018

Acta Biochim Pol

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“…As the most potent pro-angiogenic factor recognized internationally so far, VEGF can enhance the microvascular permeability, increase the release of tissue factors and proteases and stimulate division of endothelial cells. TGF-β1 directly regulates VEGF expression and participates in CNV (19)(20)(21). According to the results in this study, obviously reduced concentrations of serum VEGF and TGF-β1 were observed after combination therapy, implying that the disease is controlled efficiently, and the visual acuity is improved.…”

Section: Discussionmentioning

confidence: 57%

Efficacy of ranibizumab combined with photodynamic therapy on wet age‑related macular degeneration

Chen

Wang

Cui³

et al. 2020

Exp Ther Med

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Efficacy and safety of intravitreal ranibizumab (IVR) combined with photodynamic therapy (PDT) in treating wet age-related macular degeneration (wAMD) were studied. A total of 130 eyes were collected from 130 wAMD patients treated in Affiliated to Qingdao University Yuhuangding Hospital of Yantai, of which 65 were given IVR combined with PDT (combination therapy group) and the remaining 65 were treated with simple IVR (ranibizumab group). The differences in best corrected visual acuity (BCVA), central macular thickness (CMT), intraocular pressure, choroidal neovascularization (CNV) leakage, levels of serum vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) as well as complication rate were compared before and after treatment between the two groups. At 1, 3, 6 and 12 months after treatment, combination therapy group had remarkably better BCVA and notably smaller CMT than ranibizumab group. Fundus fluorescein angiography (FFA) showed that the area of macular degeneration was reduced markedly after treatment in both groups, and the area in combination therapy group was evidently smaller than that in ranibizumab group at 1, 3 and 6 months after treatment. At 3 months after treatment, the levels of serum VEGF and TGF-β1 declined obviously in the two groups compared with those before treatment. The IVR combined with PDT can effectively improve the visual acuity, decrease CMT and prominently reduce the area of macular degeneration of wAMD patients, and its therapeutic effects are long-standing and tolerable for the patients, so it is worthy of clinical popularization.

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“…Aflibercept and ranibizumab are recombinant humanized monoclonal antibodies that inactivate VEGF (22). VEGF is a potent angiogenic factor, the overexpression of which is known to deteriorate AMD (23). TGF-β1, a critical regulator in various physiological and pathological processes, stimulates endothelial cells to synthesize as well as secrete VEGF.…”

Section: Discussionmentioning

confidence: 99%

Role of inflammatory factors in the effects of aflibercept or ranibizumab treatment for alleviating wet age‑associated macular degeneration

Yuan

2019

Exp Ther Med

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Aflibercept and ranibizumab are novel drugs for effectively treating wet age-associated macular degeneration (AMD). In the present study, the effect of aflibercept and ranibizumab on wet AMD was compared. A total of 80 AMD patients were intravitreously treated with aflibercept (2.0 mg/dose, 40 participants) or ranibizumab (0.3 mg/dose, 40 participants). The mean visual acuity and central subfield thickness (CTS) were determined at baseline and each follow-up visit (every 4 weeks). ELISA was used to detect the expression of transforming growth factor-β1 (TGF-β1), monocyte chemoattractant protein 1 (MCP-1) and interleukin 6 (IL-6). The primary outcome was the mean change in visual acuity letter score (VAS) and CTS at 1 year. The VAS was markedly improved by 13.1 in the aflibercept group and by 11.0 in the ranibizumab group. In a subgroup of patients with an initial VAS of <69, the mean improvement in the VAS was 17.7 in the aflibercept group and 13.2 in the ranibizumab group (P<0.01). The mean CTS was markedly decreased by 141 in the aflibercept group and by 134 in the ranibizumab group. In the subgroup of patients with an initial VAS of <69, the mean CTS was decreased by 171 in the aflibercept group and by 154 in the ranibizumab group (P<0.01). However, the change of VAS and CTS was similar between the ranibizumab and aflibercept groups when the initial VAS was ≥69. No significant differences in serious adverse events were identified between the aflibercept and ranibizumab groups. The levels of TGF-β1, IL-6 and MCP-1 were decreased by the aflibercept and ranibizumab treatments. The decrease in the levels of the inflammatory factors was more obvious in patients with an initial VAS of <69 in comparison with that in patients with an initial VAS of ≥69. Negative correlations between the levels of TGF-β1, MCP-1 and IL-6 and the mean change of VAS when patients were treated with aflibercept or ranibizumab were identified among all ages. Positive correlations between the levels of TGF-β1, MCP-1 and IL-6 and the mean change of CTS were observed when the initial VAS of the patients was <69. In conclusion, the efficacy of aflibercept in treating patients with AMD was better than that of ranibizumab when the initial VAS of the patients was <69. The inhibition of inflammatory factors may be a secondary effect of aflibercept and ranibizumab treatment. The present study provides a useful reference for the clinical treatment of wet AMD (Chinese Clinical Trial Registry no. ChiCTR1800017782).

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HTRA1 and TGF-β1 Concentrations in the Aqueous Humor of Patients With Neovascular Age-Related Macular Degeneration

Abstract: In nCNV patients, HTRA1 and TGF-β1 were significantly higher compared to controls. After treatment, TGF-β1 was persistently elevated, while HTRA1 returned to control levels, suggesting the involvement of TGF-β1 and HTRA1 in neovascular AMD and a VEGFA-independent role for TGF-β1.

Cited by 49 publications

References 30 publications

Immune response against HtrA proteases in children with cutaneous mastocytosis

Immune response against HtrA proteases in children with cutaneous mastocytosis

Efficacy of ranibizumab combined with photodynamic therapy on wet age‑related macular degeneration

Role of inflammatory factors in the effects of aflibercept or ranibizumab treatment for alleviating wet age‑associated macular degeneration

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