scholarly journals Therapeutic Effects of Topical Netrin-4 Inhibits Corneal Neovascularization in Alkali-Burn Rats

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0122951 ◽  
Author(s):  
Yun Han ◽  
Yi Shao ◽  
Tingting Liu ◽  
Yang-Luowa Qu ◽  
Wei Li ◽  
...  
Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 647
Author(s):  
Henry T. Hsueh ◽  
Yoo-Chun Kim ◽  
Ian Pitha ◽  
Matthew D. Shin ◽  
Cynthia A. Berlinicke ◽  
...  

Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life.


2019 ◽  
Vol 38 (4) ◽  
pp. 315-321 ◽  
Author(s):  
Kyung Eun Han ◽  
Mi Hye Park ◽  
Kyoung Hye Kong ◽  
Euno Choi ◽  
Kyu-Ryong Choi ◽  
...  

2018 ◽  
Vol 59 (5) ◽  
pp. 2133 ◽  
Author(s):  
Mingjun Tang ◽  
Ying Yang ◽  
Jingzhi Yu ◽  
Jin Qiu ◽  
Pei Chen ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Sertan Goktas ◽  
Ender Erdogan ◽  
Rabia Sakarya ◽  
Yasar Sakarya ◽  
Mustafa Yılmaz ◽  
...  

Objective. To investigate the effects of topical and subconjunctival tigecycline on the prevention of corneal neovascularization.Materials and Methods. Following chemical burn, thirty-two rats were treated daily with topical instillation of 1 mg/mL tigecycline (group 1) or subconjunctival instillation of 1 mg/mL tigecycline (group 3) for 7 days. Control rats received topical (group 2) or subconjunctival (group 4) 0.9% saline. Digital photographs of the cornea were taken on the eighth day after treatment and analyzed to determine the percentage area of the cornea covered by neovascularization. Corneal sections were analyzed histopathologically.Results. The median percentages of corneal neovascularization in groups 1 and 3 were 48% (95% confidence interval (CI), 44.2–55.8%) and 33.5% (95% CI, 26.6–39.2%), respectively. The median percentages of corneal neovascularization of groups 1 and 3 were significantly lower than that of the control group (P=0.03andP<0.001, resp.). Histologic examination of samples from groups 1 and 3 showed lower vascularity than that of control groups.Conclusion. Topical and subconjunctival administration of tigecycline seems to be showing promising therapeutic effects on the prevention of corneal neovascularization. Furthermore, subconjunctival administration of tigecycline is more potent than topical administration in the inhibition of corneal neovascularization.


2011 ◽  
Vol 46 (2) ◽  
pp. 66-72 ◽  
Author(s):  
Ye Wang ◽  
Hongmei Yin ◽  
Peng Chen ◽  
Lixin Xie ◽  
Yiqiang Wang

2008 ◽  
Vol 49 (5) ◽  
pp. 2172 ◽  
Author(s):  
Hiroshi Mochimaru ◽  
Tomohiko Usui ◽  
Tomonori Yaguchi ◽  
Yasuharu Nagahama ◽  
Go Hasegawa ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dong Hyun Kim ◽  
Sang-Taek Im ◽  
Jin Young Yoon ◽  
Seunghoon Kim ◽  
Mee Kum Kim ◽  
...  

AbstractWe compared the therapeutic effects of topical 8-oxo-2′-deoxyguanosine (8-oxo-dG) and corticosteroid in a murine ocular alkali burn model. (n = 128) The corneal alkali burn model was established by applying 0.1 N sodium hydroxide (NaOH), followed by treatment with 8-oxo-dG, 0.1% fluorometholone (FML), 1% prednisolone acetate (PDE), or phosphate-buffered saline (PBS) twice daily. One week later, the clinical and histological status of the cornea were assessed. Transcript levels of inflammatory cytokines and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as well as the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the cornea, were assayed. The 8-oxo-dG and PDE groups showed marked improvements in corneal integrity and clarity when compared with the PBS group (each p < 0.01). The numbers of cells stained for neutrophil elastase and F4/80-positive inflammatory cells were significantly decreased, with levels of interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, and total ROS/RNS amounts markedly reduced in the 8-oxo-dG, FML, and PDE groups (each p < 0.05). Levels of NADPH oxidase type 2 and 4 were substantially more repressed in the 8-oxo-dG-treated group than in the PDE-treated group (each p < 0.05). Topical 8-oxo-dG showed excellent therapeutic effects that were comparable with those treated with topical PDE in a murine ocular alkali burn model.


2017 ◽  
Vol 01 (01) ◽  
Author(s):  
Amany Abd El Fattah El Shazly ◽  
Asmaa Ibrahim Ahmed ◽  
Yasser Abdelmageuid Elzankalony ◽  
Walid Mohamed Abd El Raouf El Zawahry

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Shanshan Wan ◽  
Wanju Yang ◽  
Yumiao Pan ◽  
Zhuoqun Rao ◽  
Yanning Yang

Background. G9a, a well-known methyltransferase, plays a vital role in biological processes. However, its role in corneal neovascularization (CoNV) remains unclear. Methods. In vitro and in vivo models were assessed in hypoxia-stimulated angiogenesis and in a mouse model of alkali burn-induced CoNV. Human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic conditions and different reoxygenation times to identify the molecular mechanisms involved in this process. Results. In this study, we found that G9a was positively related to corneal alkali burn-induced injury. Inhibition of G9a with BIX 01294 (BIX) alleviated corneal injury, including oxidative stress and neovascularization in vivo. Similarly, inhibition of G9a with either BIX or small interfering RNA (siRNA) exerted an inhibitory effect on hypoxia/reoxygenation (H/R)-induced oxidative stress and angiogenesis in HUVECs. Moreover, our study revealed that ablation of reactive oxygen species (ROS) with N-acetyl-cysteine suppressed angiogenesis in HUVECs exposed to H/R stimulation. Furthermore, NADPH oxidase 4 (Nox4), which was positively associated with ROS production and angiogenesis, was elevated during H/R. This effect could be reversed through suppression of the transcription activity of G9a with BIX or siRNA. In addition, the Nrf2/HO-1 pathway, upstream of Nox4, was activated in both BIX-treated mice and G9a-inhibited HUVECs. Collectively, our results demonstrated that inhibition of G9a-alleviated corneal angiogenesis by inhibiting Nox4-dependent ROS production through the Nrf2/HO-1 signaling pathway. These findings indicate that G9a may be a valuable therapeutic target for CoNV.


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