Imbalance of Matrix Metalloproteinases and Their Inhibitors Is Correlated With Trabeculectomy Outcomes in Acute Primary Angle Closure

Qian, Tianwei; Fu, Mingshui; Hu, Chunling; Zhang, Zhihua; Xu, Xun; Zou, Haidong

doi:10.1016/j.ajo.2019.12.014

Cited by 7 publications

(10 citation statements)

References 34 publications

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“…For example, elucidating changes in AH in later stages of disease could lead to improved outcomes for glaucoma filtration surgeries in later-stage patients, since failure of filtering blebs may be linked to constant exposure to profibrotic mediators like TIMPs in glaucomatous AH. 13,41,71,72 Eyes with ADAMTS10-OAG, on the other hand, were sampled relatively early in the course of disease (mean IOP in the group was 19.7 mmHg, as compared to 54.9 mmHg for dogs with CPACG). These dogs, along with heterozygote and wild-type counterpart Beagles, were markedly younger than the pet dogs with and without CPACG sampled for the other arm of the study.…”

Section: Discussionmentioning

confidence: 99%

“…Myocilin, an ECM glycoprotein implicated in human glaucomas, also seems to be increased in the TM and AH of dogs with CPACG 31,32,34 . Most importantly, MMPs and TIMPs are believed to be the primary regulators of ECM modification in people, and alterations in MMPs and TIMPs in AH have been shown in people and dogs with PACG 9,35–41 . We recently found that multiple MMPs and TIMPs were significantly increased in AH from dogs with CPACG when compared with AH from companion dogs without overt evidence of CPACG, with disproportionate increases in MMP‐8 and TIMP‐2 42 …”

Section: Introductionmentioning

confidence: 96%

“…31,32,34 Most importantly, MMPs and TIMPs are believed to be the primary regulators of ECM modification in people, and alterations in MMPs and TIMPs in AH have been shown in people and dogs with PACG. 9,[35][36][37][38][39][40][41] We recently found that multiple MMPs and TIMPs were significantly increased in AH from dogs with CPACG when compared with AH from companion dogs without overt evidence of CPACG, with disproportionate increases in MMP-8 and TIMP-2. 42 The functional implication of alterations in MMPs and TIMPs in AH from dogs with CPACG remains unclear, particularly as the most recent study found both MMPs and TIMPs to be increased, which would seem contradictory.…”

Section: Introductionmentioning

confidence: 99%

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Relative ability of aqueous humor from dogs with and without primary angle‐closure glaucoma and ADAMTS10 open‐angle glaucoma to catalyze or inhibit collagenolysis

Pumphrey,

Harman,

Anderson

et al. 2023

Veterinary Ophthalmology

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ObjectiveThe objective of the study was to compare the ability of aqueous humor (AH) from dogs with primary angle‐closure glaucoma (CPACG), companion dogs without overt evidence of CPACG, and Beagles with and without ADAMTS10 open‐angle glaucoma (ADAMTS10‐OAG) to catalyze or inhibit collagenolysis.Animals studiedSeventeen normal pet dogs, 27 dogs with CPACG, 19 Beagles with ADAMTS10‐OAG, and 4 unaffected Beagles.ProceduresA fluorescein‐based substrate degradation assay was used to assess AH proteolytic capacity. Samples were then assayed using the same substrate degradation assay, with recombinant activated matrix metalloproteinase‐2 (MMP‐2) added to measure protease inhibition effects.ResultsFor the protease activity assay, relative fluorescence (RF) for AH from normal pet dogs was 13.28 ± 2.25% of control collagenase while RF for AH from dogs with CPACG was 17.47 ± 4.67%; RF was 8.57 ± 1.72% for ADAMTS10‐OAG Beagles and 7.99 ± 1.15% for unaffected Beagles. For the MMP‐2 inhibition assay, RF for AH from normal dogs was 34.96 ± 15.04% compared to MMP‐2 controls, while RF from dogs with CPACG was 16.69 ± 7.95%; RF was 85.85 ± 13.23% for Beagles with ADAMTS10‐OAG and 94.51 ± 8.36% for unaffected Beagles. Significant differences were found between dogs with CPACG and both normal pet dogs and dogs with ADAMTS10‐OAG and between normal pet dogs and both groups of Beagles.ConclusionsAH from dogs with CPACG is significantly more able to catalyze proteolysis and inhibit MMP‐2 than AH from normal dogs or dogs with ADAMTS10‐OAG. Results suggest that pathogenesis may differ between CPACG and ADAMTS10‐OAG.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relative ability of aqueous humor from dogs with and without primary angle‐closure glaucoma and ADAMTS10 open‐angle glaucoma to catalyze or inhibit collagenolysis

Pumphrey,

Harman,

Anderson

et al. 2023

Veterinary Ophthalmology

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“…One experienced surgeon (MF) performed a trabeculectomy in all patients included in this study, and the main steps of the operation were similar to those described in our previous study. 23 Under topical gel anesthesia, the surgeon created a fornix-based conjunctival flap from 11 to 1 o'clock, followed by dissection of a limbus-based 4 × 4-mm scleral flap. A sponge soaked with 5-fluorouracil (25 mg/mL) was placed underneath the conjunctival flap for 3 minutes, followed by irrigation of the surgical area with balanced salt solution.…”

Section: Methodsmentioning

confidence: 99%

Aqueous Humor Growth Factor Levels and Trabeculectomy Outcomes in Primary Open-Angle Glaucoma Patients: A 2-Year Prospective Study

Qian

et al. 2022

Trans. Vis. Sci. Tech.

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Purpose Maintenance of a filtering bleb is essential for long-term intraocular pressure control after trabeculectomy. Surgical site fibrosis and excessive extracellular matrix production are common causes of trabeculectomy failure, mediated by several growth factors. We aimed to evaluate the levels of five growth factors and their correlation with trabeculectomy outcomes in patients with primary open-angle glaucoma (POAG). Methods We collected aqueous humor samples intraoperatively from patients with POAG who underwent trabeculectomy and measured the concentrations of transforming growth factor-β (TGF-β), acidic fibroblast growth factor (aFGF), insulin-like growth factor-1, vascular endothelial growth factor, and platelet-derived growth factor using multiplexed immunoassay kits. Intraocular pressure was measured with Goldmann applanation tonometry at 1 week and at 1, 3, 6, 12, 18, and 24 months after trabeculectomy. We allocated the eyes based on surgical outcome into a success or failure group. Results Significantly high levels of aFGF and TGF-β were observed in the failure group (both P < 0.0001) and were significant risk factors for trabeculectomy outcomes. Higher success rates were observed over the 24-month follow-up period in eyes with low aFGF and TGF-β levels compared to eyes with high levels ( P = 0.0031 and P = 0.0007, respectively). The levels of TGF-β were significantly positively correlated with aFGF. Conclusions In POAG patients, high aFGF and TGF-β levels were significant risk factors for trabeculectomy failure. Translational Relevance Modulation of aFGF and TGF-β expression may have potential clinical applications after filtration surgery.

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“…For all the prior APAC patients, trabeculectomy was performed by one experienced surgeon (M. Fu). The surgical process was described in our prior study (Qian et al 2020). Briefly, a fornix-based conjunctival flap was made, a limbus-based 4 9 4-mm scleral flap was dissected, and a 5-fluorouracil-soaked sponge (25 mg/ml) was placed underneath the conjunctival flap for 3 min.…”

Section: Surgical Technique and Postoperative Carementioning

confidence: 99%

Inflammatory cytokines levels in aqueous humour and surgical outcomes of trabeculectomy in patients with prior acute primary angle closure

Qian

Gong

et al. 2021

Acta Ophthalmologica

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To quantify the levels of three inflammatory cytokines in the aqueous humour of patients with prior acute primary angle closure (APAC) and investigate their correlation with surgical outcomes of trabeculectomy. Methods: In this prospective cohort study, aqueous humour samples were collected from 44 prior APAC eyes. Analyte concentrations of monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) were measured using multiplexed immunoassay kits. Intraocular pressure was measured using Goldmann application tonometry. Results: Forty-four prior APAC eyes were followed up for 24 months after trabeculectomy and divided into success and failure groups according to surgical outcomes. Monocyte chemoattractant protein-1 (MCP-1) levels in the aqueous humour were significantly higher in the failure group (p = 0.0118). Univariate and multivariate analyses showed that MCP-1 level was a significant risk factor for trabeculectomy outcomes (univariate analysis: p = 0.016, odds ratio = 14.538; multivariate analysis: p = 0.023, odds ratio = 13.718). When prior APAC eyes were divided according to MCP-1 levels, the overall success rate was significantly higher in eyes with low MCP-1 levels than eyes with high MCP-1 levels (p = 0.0249). Conclusion:In prior APAC patients, the MCP-1 level in the aqueous humour predicts trabeculectomy results. Therefore, modulation of MCP-1 expression may have potential clinical applications after filtration surgery.

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Imbalance of Matrix Metalloproteinases and Their Inhibitors Is Correlated With Trabeculectomy Outcomes in Acute Primary Angle Closure

Cited by 7 publications

References 34 publications

Relative ability of aqueous humor from dogs with and without primary angle‐closure glaucoma and ADAMTS10 open‐angle glaucoma to catalyze or inhibit collagenolysis

Relative ability of aqueous humor from dogs with and without primary angle‐closure glaucoma and ADAMTS10 open‐angle glaucoma to catalyze or inhibit collagenolysis

Aqueous Humor Growth Factor Levels and Trabeculectomy Outcomes in Primary Open-Angle Glaucoma Patients: A 2-Year Prospective Study

Inflammatory cytokines levels in aqueous humour and surgical outcomes of trabeculectomy in patients with prior acute primary angle closure

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