scholarly journals Eye Drops of Metformin Prevents Fibrosis After Glaucoma Filtration Surgery in Rats via Activating AMPK/Nrf2 Signaling Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Xueru Li ◽  
Yu Leng ◽  
Qingzhi Jiang ◽  
Ziwen Wang ◽  
Peng Luo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Eye Drops ◽  
Filtration Surgery ◽  
Glaucoma Filtration Surgery ◽  
Nrf2 Signaling Pathway

scholarly journals Avoiding BAK in postoperative eye drops reduces the need for subconjunctival 5-FU injections post-trabeculectomy

2020 ◽  
Vol 17 (1) ◽  
pp. 128-131
Author(s):  
Keith Ong ◽  
Leonard Ong
Keyword(s):  
Intraocular Pressure ◽  
Mitomycin C ◽  
T Test ◽  
Topical Steroids ◽  
Eye Drops ◽  
Filtration Surgery ◽  
Glaucoma Filtration Surgery ◽  
Group A ◽  
Group B ◽  
Causes Of Failure

Purpose: Subconjunctival fibrosis is one of the main causes of failure of glaucoma filtration surgery. It can result in absence of a filtration bleb, a small scarred bleb, or a cystic bleb. 5-Fluorouracil (5-FU), mitomycin C (MMC), and topical steroids have been used to suppress subconjunctival fibrosis. Method: A study was done analyzing the number of postoperative subconjunctival 5-FU injections for trabeculectomy on pseudophakic eyes prior to and following the change to a BAK-free regimen. The cohort consisted of 16 consecutive cases undergoing primary trabeculectomy without intraoperative MMC or 5-FU. The trabeculectomy surgery included a groove sclerectomy procedure. Group A were 8 eyes of patients who had the author’s standard Chlorsig, Maxidex, and Prednefrin Forte eye drops tds. Group B were 8 eyes who had Chlorsig-dexamethasone and Optive-dexamethasone tds eye drops postoperatively. Results: Group B (BAK-free) patients required fewer postoperative 5-FU subconjunctival injections (average: 2.9, range: 1-5 injections) compared to Group A (BAK) patients (average: 7.3, range: 4-18 injections). This difference was statistically significant (P = 0.02, unpaired t-test). All patients had functioning blebs and did not require glaucoma medications to maintain target intraocular pressure. The Group B (BAK-free) patients had more diffuse blebs than the Group A (BAK) patients. Conclusion: The results demonstrated that when BAK was eliminated from postoperative eye drops in trabeculectomy, the number of postoperative 5-FU injections was reduced.

scholarly journals Pluripotent epigenetic regulator OBP-801 maintains filtering blebs in glaucoma filtration surgery model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yuji Yamamoto ◽  
Atsushi Mukai ◽  
Toru Ikushima ◽  
Yasuo Urata ◽  
Shigeru Kinoshita ◽  
...  
Keyword(s):  
Wound Healing ◽  
Rabbit Model ◽  
Vehicle Control ◽  
Control Group ◽  
Eye Drops ◽  
Subconjunctival Injection ◽  
Filtration Surgery ◽  
Glaucoma Filtration Surgery ◽  
Vehicle Control Group ◽  
Epigenetic Regulator

AbstractInhibition of fibrosis is indispensable for maintaining filtering blebs after glaucoma filtration surgery (GFS). The purpose of this study was to investigate the ability of a pluripotent epigenetic regulator OBP-801 (OBP) to ameliorate extracellular matrix formation in a rabbit model of GFS. Rabbits that underwent GFS were treated with OBP. The gene expression profiles and intraocular pressure (IOP) were monitored until 30 postoperative days. The bleb tissues were evaluated for tissue fibrosis at 30 postoperative days. In in vitro models, OBP interfered the functions of diverse genes during the wound-healing process. In in vivo GFS models, the expressions of TGF-β3, MMP-2, TIMP-2 and 3, LOX, COL1A and SERPINH1 were significantly inhibited at 30 postoperative days in the OBP group compared with those in the vehicle control group. OBP treatment involving subconjunctival injection or eye drops showed no adverse effects, and reduced levels of α-SMA and collagen deposition at the surgical wound site. OBP maintained the long-lived bleb without scar formation, and IOP was lower at 30 postoperative days compared with the vehicle control group. These findings suggest that OBP is an effective and useful candidate low-molecular-weight agent for improving wound healing and surgical outcomes in a rabbit model of GFS.

scholarly journals Effects of Regorafenib, a Multi-Kinase Inhibitor, on Conjunctival Scarring in a Canine Filtration Surgery Model in Comparison with Mitomycin-C

2019 ◽  
Vol 21 (1) ◽  
pp. 63
Author(s):  
Emika Nemoto ◽  
Shota Kojima ◽  
Tetsuya Sugiyama ◽  
Denan Jin ◽  
Shinji Takai ◽  
...  
Keyword(s):  
Mitomycin C ◽  
Kinase Inhibitor ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Eye Drops ◽  
Filtration Surgery ◽  
Glaucoma Filtration Surgery ◽  
Significant Difference ◽  
Bleb Formation ◽  
Collagen Density

Regorafenib eye drops were developed for treating age-related macular degeneration. This study aimed to investigate the effects of this multi-kinase inhibitor on intraocular pressure (IOP), bleb formation, and conjunctival changes in a canine filtration surgery model. Glaucoma filtration surgery models were created in 24 eyes of 24 beagles. In experiment 1 (Ex 1), regorafenib eye drops (regorafenib group: n = 6) or a vehicle (control group, n = 6) were instilled twice daily for 4 weeks postoperatively. In experiment 2 (Ex 2), regorafenib eye drops were instilled as in Ex 1 (regorafenib group: n = 6) for 12 weeks while conventional intraoperative mitomycin-C (MMC) was utilized (MMC group: n = 6), In Ex 1, only the regorafenib group showed significant IOP reduction with a significantly higher bleb score. Subconjunctival area, collagen density, vessels, and cells showing proliferation and differentiation were lower in subconjunctival tissue in the regorafenib group. In Ex 2, no significant difference was found in IOP reduction and bleb formation between the regorafenib and MMC groups; bleb walls were significantly thicker and collagen density and vessels were higher in the regorafenib group; and no differences were observed in the above-mentioned cells. Thus, regorafenib might be a better alternative to MMC for creating thicker and less ischemic blebs in glaucoma filtration surgery.

Comparison of phaco time parameters in eyes with and without glaucoma filtration surgery due to pseudoexfoliation glaucoma

2021 ◽  
pp. 112067212110177
Author(s):  
Ayse Gul Kocak Altintas ◽  
Cagri Ilhan
Keyword(s):  
Clinical Characteristics ◽  
Pseudoexfoliation Glaucoma ◽  
Filtration Surgery ◽  
Glaucoma Filtration Surgery ◽  
Mean Values ◽  
Time Parameters ◽  
The Mean ◽  
Group 2 ◽  
Surgical Manipulations ◽  
Phaco Time

Purpose: To compare the phaco time parameters including ultrasound time (UST), effective phaco time (EPT), and average phaco power (APP) in eyes with pseudoexfoliation glaucoma (PEG) and had or had not glaucoma filtration surgery. Methods: In this retrospective comparative study, Group 1 was constructed with 84 PEG patients who had not operated previously, and Group 2 was constructed with 49 PEG patients who had glaucoma filtration surgery. The mean values of UST, EPT, and APP were compared. The preoperative clinical characteristics and surgical manipulations were also compared. Results: The mean ages and male-to-female ratios of the groups were similar ( p > 0.05, for both). There was no difference in the preoperative clinical characteristics, including biometric values between the groups ( p > 0.05, for all). Some surgical manipulations, including pupillary stretching ( p = 0.004), pupillary membrane peeling ( p = 0.021), iris hook using ( p = 0.041), and capsular tension ring implantation ( p = 0.041), were significantly performed more commonly in Group 2. Although the mean UST and EPT values were similar ( p > 0.05, for both), the mean APP value was significantly lower in Group 2 ( p = 0.011). Conclusion: The lower APP parameter was observed in PEG patients having had glaucoma filtration surgery. Needing more surgical manipulation to overcome poor pupillary dilation and weak zonular instability can be a reason for this result.

scholarly journals Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice

2021 ◽  
Vol 22 (11) ◽  
pp. 5995
Author(s):  
Chand Basha Davuljigari ◽  
Frederick Adams Ekuban ◽  
Cai Zong ◽  
Alzahraa A. M. Fergany ◽  
Kota Morikawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Messenger Rna ◽  
Hepatic Necrosis ◽  
Related Factor ◽  
Necrosis Factor Alpha ◽  
Adult Mice ◽  
Nrf2 Signaling Pathway ◽  
Antioxidant Proteins ◽  
Oxide Synthase

Acrylamide is a well characterized neurotoxicant known to cause neuropathy and encephalopathy in humans and experimental animals. To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in acrylamide-induced neuropathy, male C57Bl/6JJcl adult mice were exposed to acrylamide at 0, 200 or 300 ppm in drinking water and co-administered with subcutaneous injections of sulforaphane, a known activator of the Nrf2 signaling pathway at 0 or 25 mg/kg body weight daily for 4 weeks. Assessments for neurotoxicity, hepatotoxicity, oxidative stress as well as messenger RNA-expression analysis for Nrf2-antioxidant and pro-inflammatory cytokine genes were conducted. Relative to mice exposed only to acrylamide, co-administration of sulforaphane protected against acrylamide-induced neurotoxic effects such as increase in landing foot spread or decrease in density of noradrenergic axons as well as hepatic necrosis and hemorrhage. Moreover, co-administration of sulforaphane enhanced acrylamide-induced mRNA upregulation of Nrf2 and its downstream antioxidant proteins and suppressed acrylamide-induced mRNA upregulation of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS) in the cerebral cortex. The results demonstrate that activation of the Nrf2 signaling pathway by co-treatment of sulforaphane provides protection against acrylamide-induced neurotoxicity through suppression of oxidative stress and inflammation. Nrf2 remains an important target for the strategic prevention of acrylamide-induced neurotoxicity.

scholarly journals Sulforaphane induces colorectal cancer cell proliferation through Nrf2 activation in a p53-dependent manner

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Yunjeong Gwon ◽  
Jisun Oh ◽  
Jong-Sang Kim
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Related Factor ◽  
Mild Stress ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Nrf2 Signaling Pathway ◽  
Dose Dependent

AbstractSulforaphane is a well-known phytochemical that stimulates nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant cellular response. In this study, we found that sulforaphane promoted cell proliferation in HCT116 human colon cancer cells expressing a normal p53 gene in a dose-dependent but biphasic manner. Since p53 has been reported to contribute to cell survival by regulating various metabolic pathways to adapt to mild stress, we further examined cellular responses in both p53-wild-type (WT) and p53-knockout (KO) HCT116 cells exposed to sulforaphane in vitro and in vivo. Results demonstrated that sulforaphane treatment activated Nrf2-mediated antioxidant enzymes in both p53-WT and p53-KO cells, decreased apoptotic protein expression in WT cells but increased in KO cells in a dose-dependent manner, and increased the expression of a mitochondrial biogenesis marker PGC1α in WT cells but decreased in KO cells. Moreover, a low dose of sulforaphane promoted tumor growth, upregulated the Nrf2 signaling pathway, and decreased apoptotic cell death in p53-WT HCT116 xenografts compared to that in p53-KO HCT116 xenografts in BALB/c nude mice. These findings suggest that sulforaphane can influence colon cancer cell proliferation and mitochondrial function through a crosstalk between the Nrf2 signaling pathway and p53 axis.

scholarly journals Melatonin Promotes In Vitro Maturation of Vitrified-Warmed Mouse Germinal Vesicle Oocytes, Potentially by Reducing Oxidative Stress through the Nrf2 Pathway

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2324
Author(s):  
Shichao Guo ◽  
Jinyu Yang ◽  
Jianpeng Qin ◽  
Izhar Hyder Qazi ◽  
Bo Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
In Vitro Maturation ◽  
Germinal Vesicle ◽  
Melatonin Receptors ◽  
Development Rates ◽  
Nrf2 Signaling Pathway ◽  
Mouse Gv Oocytes ◽  
Intracellular Oxidative Stress

Previously it was reported that melatonin could mitigate oxidative stress caused by oocyte cryopreservation; however, the underlying molecular mechanisms which cause this remain unclear. The objective was to explore whether melatonin could reduce oxidative stress during in vitro maturation of vitrified-warmed mouse germinal vesicle (GV) oocytes through the Nrf2 signaling pathway or its receptors. During in vitro maturation of vitrified-warmed mouse GV oocytes, there were decreases (p < 0.05) in the development rates of metaphase I (MI) oocytes and metaphase II (MII) and spindle morphology grades; increases (p < 0.05) in the reactive oxygen species (ROS) levels; and decreases (p < 0.05) in expressions of Nrf2 signaling pathway-related genes (Nrf2, SOD1) and proteins (Nrf2, HO-1). However, adding 10−7 mol/L melatonin to both the warming solution and maturation solutions improved (p < 0.05) these indicators. When the Nrf2 protein was specifically inhibited by Brusatol, melatonin did not increase development rates, spindle morphology grades, genes, or protein expressions, nor did it reduce vitrification-induced intracellular oxidative stress in GV oocytes during in vitro maturation. In addition, when melatonin receptors were inhibited by luzindole, the ability of melatonin to scavenge intracellular ROS was decreased, and the expressions of genes (Nrf2, SOD1) and proteins (Nrf2, HO-1) were not restored to control levels. Therefore, we concluded that 10−7 mol/L melatonin acted on the Nrf2 signaling pathway through its receptors to regulate the expression of genes (Nrf2, SOD1) and proteins (Nrf2, HO-1), and mitigate intracellular oxidative stress, thereby enhancing in vitro development of vitrified-warmed mouse GV oocytes.

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