scholarly journals The Effects of Rebamipide 2% Ophthalmic Solution Application on Murine Subbasal Corneal Nerves After Environmental Dry Eye Stress

2019 ◽  
Vol 20 (16) ◽  
pp. 4031
Author(s):  
Cem Simsek ◽  
Takashi Kojima ◽  
Shigeru Nakamura ◽  
Murat Dogru ◽  
Kazuo Tsubota
Keyword(s):  
Dry Eye ◽  
Ophthalmic Solution ◽  
Inflammatory Cells ◽  
Office Workers ◽  
Therapeutic Effects ◽  
Fiber Density ◽  
Neuroprotective Effects ◽  
Staining Score ◽  
Corneal Nerves

Rebamipide ophthalmic solution is a mucin secretagogue which is an important therapeutic agent in the treatment of dry eye. It has been noted that dry eye in office workers is associated with a decrease in secretory mucin. This study aimed to evaluate the effects of 2% rebamipide ophthalmic solution in mice subjected to environmental dry eye stress (EDES), which mimics the conditions of office workers. Thirty eyes from thirty BALB/c mice (eight-week-old males) were divided into three treatment groups: artificial tear (vehicle), 2% rebamipide ophthalmic solution, and 0.1% hyaluronic acid (HA) ophthalmic solution. After four days of pretreatment, mice were exposed to EDES for three days. The corneal subbasal nerve and inflammatory cells were then examined using in vivo confocal microscopy. Following EDES exposure, the lissamine green staining score was significantly lower and corneal sensitivity was more preserved in the 2% rebamipide group than in the HA group. In addition, the subbasal nerve fiber density was significantly higher and the DC density was significantly lower in the 2% rebamipide group than in the HA group. Overall, the topical rebamipide ophthalmic solution showed more favorable therapeutic effects when compared to the HA ophthalmic solution in a mouse model of EDES, likely owing to its anti-inflammatory and neuroprotective effects.

scholarly journals Ultrasound-assisted gatifloxacin delivery in mouse cornea, in vivo

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Uk Jegal ◽  
Jun Ho Lee ◽  
Jungbin Lee ◽  
Hyerin Jeong ◽  
Myoung Joon Kim ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Ophthalmic Solution ◽  
Ultrasound Treatment ◽  
Ocular Infection ◽  
Therapeutic Effects ◽  
Corneal Surface ◽  
Ultrasound Waves ◽  
Two Photon Microscopy ◽  
Two Photon

Abstract Gatifloxacin is a 4th generation fluoroquinolone antibiotic used in the clinic to treat ocular infection. One limitation of gatifloxacin is its relatively poor corneal penetration, and the increase of its trans-corneal delivery would be beneficial to reduce the amount or frequency of daily dose. In this study, ultrasound treatment was applied to enhance the trans-corneal delivery of gatifloxacin without damage. Experiments were conducted on mouse eyes in ex vivo and in vivo conditions. Ultrasound waves with 1 MHz in frequency, 1.3 W/cm2 in intensity were applied onto the mouse cornea for 5 minutes, and then gatifloxacin ophthalmic solution was instilled and left there for 10 minutes. 3D gatifloxacin distribution in the cornea was measured by two-photon microscopy (TPM) imaging based on its intrinsic fluorescence. Longitudinal TPM imaging of ultrasound treated mouse corneas showed the increase of initial gatifloxacin intensities on the corneal surface compared to untreated mouse corneas by 67%, and then the increased gatifloxacin delivery into the cornea from the surface at later time. The delivered gatifloxacin in the corneal epithelium stayed longer in the ultrasound treated corneas than in the untreated corneas. The enhanced trans-corneal delivery and extended stay of gatifloxacin in the mouse cornea by ultrasound treatment could be beneficial for therapeutic effects. This study demonstrated the detail process of enhanced trans-corneal gatifloxacin delivery by ultrasound treatment.

The Neuroprotective Effects of BNG-1: A New Formulation of Traditional Chinese Medicines for Stroke

2005 ◽  
Vol 33 (01) ◽  
pp. 61-71 ◽  
Author(s):  
Fong-Chi Cheng ◽  
Wen-Long Chen ◽  
Jiann-Wu Wei ◽  
Ken-Shung Huang ◽  
George G. Yarbrough
Keyword(s):  
Clinical Results ◽  
Artery Occlusion ◽  
Drug Formulation ◽  
Cerebral Stroke ◽  
Therapeutic Effects ◽  
Traditional Chinese Medicines ◽  
Neuroprotective Effects ◽  
Chinese Medicines

BNG-1, a novel mixture of traditional Chinese medicines with a long history in the treatment of stroke, exhibited acute neuroprotection effect on rats with middle cerebral artery occlusion (MCAO). Anti-ischemic effects were seen in both animals receiving BNG-1 before the ischemic insult as well as in animals receiving the drug formulation after surgical occlusion of the artery. Anti-thrombic activity was seen in vitro to inhibit arachidonic acid-induced platelet aggregation and in vivo to prolong bleeding time in mice. BNG-1 was also found to inhibit several phosphodiesterase (PDE) isoforms with potency order of the following rank: PDE 1>PDE 3>PDE 6>PDE 2>PDE 4>PDE 5. Other pre-clinical results and emerging clinical data coupled with the present findings suggest that BNG-1 may be a safe and effective therapy for both the prevention and treatment of cerebral stroke. Moreover, the fundamental cellular mechanism underlying its therapeutic effects may result from phosphodiesterase inhibition.

scholarly journals The Specific NLRP3 Antagonist IFM-514 Decreases Fibrosis and Inflammation in Experimental Murine Non-Alcoholic Steatohepatitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Sandra Torres ◽  
Maximilian J Brol ◽  
Fernando Magdaleno ◽  
Robert Schierwagen ◽  
Frank E. Uschner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Portal Pressure ◽  
Liver Steatosis ◽  
Inflammatory Cells ◽  
Therapeutic Effects ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Markers Of Inflammation

Background and Aims: Activation of the inflammasome NLRP3 (NOD-, LRR- and pyrin domain containing 3) contributes to the development of non-alcoholic fatty liver disease (NAFLD) and progression to non-alcoholic steatohepatitis (NASH). Therefore, this study explored the therapeutic effects of a novel and selective NLRP3 antagonist in a murine dietary model of NASH.Methods: Groups of 12-week-old ApoE-/- mice were fed ad lib for 7 weeks with a methionine/choline deficient (MCD) and western diet (WD). After 3 weeks of diet-induced injury, mice were injected i. p. with the NLRP3 antagonist IFM-514 (100 mg/kg body weight) or vehicle (0.5% carmellose) every day, 5 days/week for a further 4 weeks. Several markers of inflammation, fibrosis and steatosis were evaluated. Whole transcriptome sequencing and panel RNA expression analysis (NanoString) were performed.Results: IFM-514 inhibited IL-1β production in mice challenged with 20 mg/kg lipopolysaccharide, and in mouse and human inflammatory cells in vitro. IFM-514 inhibited hepatic inflammation in the in vivo non-alcoholic steatohepatitis model assessed by H&E staining and in the hepatic gene expression of inflammasome-related proinflammatory cytokines. This effect was associated with significant reduction in caspase-1 activation. Similarly, IFM-514 was efficacious in vivo in MDC-fed ApoE-/- mice, markedly reducing portal pressure, Sirius red staining and 4-hydroxyproline content compared to vehicle-treated mice. Moreover, IFM-514 significantly reduced hepatic steatosis in MCD-fed ApoE-/- mice, as evidenced by NAFLD scores, oil red O staining, hepatic triglycerides and gene expression. In WD treated animals, similar trends in inflammation and fibrosis were observed, although not sufficient IFM-514 levels were reached.Conclusion: Overall, IFM-514 reduced liver inflammation and fibrosis, with mild effects on liver steatosis in experimental murine NASH. Blocking of NLRP3 may be an attractive therapeutic approach for NASH patients.

scholarly journals In Vivo Confocal Microscopic Evaluation of Previously Neglected Oval Cells in Corneal Nerve Vortex: An Inflammatory Indicator of Dry Eye Disease

2021 ◽  
Author(s):  
Dalan Jing ◽  
Xiaodan Jiang ◽  
Yilin Chou ◽  
Shanshan Wei ◽  
Ran Hao ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Dry Eye ◽  
Inflammatory Cells ◽  
Average Density ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Oval Cells ◽  
Oval Cell ◽  
Microscopic Evaluation

Abstract To investigate association of a type of previously neglected oval cell that located in corneal vortex with dry eye disease (DED). Observational, prospective study of 168 patients with different degrees of DED. In vivo confocal microscopy was used to observe the corneal sub-basal nerves and Langerhans cells (LCs) in both corneal vortex and periphery. The bright and oval cells also be inspected in corneal vortex. An artificial intelligence (AI) technique generated the sub-basal nerve fibre parameters. Patients were divided into three different groups based on existence of inflammatory cells. Group 2 patients showed a significant increase in corneal peripheral nerve maximum length and corneal peripheral nerve average density. Patients in Group 3 had more LC numbers than others. A type of bright and oval cell was identified in the corneal vortex might be a type of immature LC and related to disease severity of DED.

Preventive and Therapeutic Effects of Ginsenoside Rb1 for Neural Injury During Cerebral Infarction in Rats

2013 ◽  
Vol 41 (02) ◽  
pp. 341-352 ◽  
Author(s):  
Zhou Jiang ◽  
Yuhui Wang ◽  
Xiaoyun Zhang ◽  
Tao Peng ◽  
Yun Lu ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Infarct Volume ◽  
Interleukin 1 ◽  
Protective Mechanism ◽  
Intragastric Administration ◽  
Therapeutic Effects ◽  
Ginsenoside Rb1 ◽  
Neural Injury ◽  
Neuroprotective Effects

To examine the preventive and therapeutic effects of ginsenoside Rb1 for neural injury during cerebral infarction, we used a middle cerebral artery occlusion (MCAO) model in rats to investigate the effects of ginsenoside Rb1 with Edaravone as a control. Ginsenoside Rb1 was given to the rats by intragastric administration either before or after the MCAO surgery to study its preventive and therapeutic effects. Ginsenoside Rb1-treated rats had a smaller infarct volume than the positive control. Interleukin-1 (IL-1), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), neurofilament (NF) and growth associated protein-43 (GAP-43) were measured to determine brain damage and the recovery of nerves. These findings suggest that ginsenoside Rb1 has neuroprotective effects in rats, and the protection efficiency is higher than Edaravone. The protective mechanism is different from Edaravone. The preventive ability of ginsenoside Rb1 is higher than its repair ability in neuroprotection in vivo.

Safety and efficacy of ALG-1007 topical ophthalmic solution – A synthetic peptide that regulates inflammation, in patients with dry eye disease: An exploratory Phase I, open-label, single-center clinical study

2020 ◽  
Vol 3 ◽  
pp. 10
Author(s):  
Richard Lindstrom ◽  
Eric Donnenfeld ◽  
Edward Holland ◽  
Vicken Karageozian ◽  
John Park ◽  
...  
Keyword(s):  
Phase I ◽  
Dry Eye ◽  
Ophthalmic Solution ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Multiple Time ◽  
Open Label ◽  
Safety And Efficacy ◽  
Treatment Groups ◽  
Staining Score

Objectives: The objective of the study was to evaluate the safety and efficacy of ALG-1007 topical ophthalmic solution in patients with dry eye disease (DED). Materials and Methods: This Phase I, prospective, open-label, 12-week study enrolled subjects ≥18 years old with symptoms of DED for at least 6 months and at least one of the following: Total ocular staining score ≥2 or tear film breakup time (TBUT) ≤7 s. Subjects were randomized to four treatment arms: 0.125%, 0.25%, 0.4%, and 0.6% ALG-1007. Subjects received the test drug, 1 drop twice daily, and were followed at multiple time points for 12 weeks. SICCA total ocular staining score, corneal and conjunctival staining score, TBUT, and subject-reported symptoms using the visual analog scale (VAS) symptom index were assessed at baseline and at every visit. The primary safety outcome was percentage and severity of adverse events (AEs). Results: Forty eyes (21 patients) were assigned randomly to four treatment groups (n = 10 per group). Improvement in TBUT, SICCA, and VAS was seen in all groups. The highest dose tested (0.6%) was compared to the lowest dose tested (0.125%) based on change from baseline for all assessments using analysis of variance. Improvement was significantly greater in 0.6% treatment group in terms of TBUT, conjunctiva staining, SICCA, burning, discomfort, photophobia, and the composite symptom score. No serious AEs were reported after 12 weeks of treatment. Conclusion: Outcome measures improved in all the treatment groups. At the highest dose, ALG-1007 demonstrated statistically significant improvement compared to the lowest dose in 7 out of 12 assessments, indicating a dose response. This suggests that the active pharmaceutical ingredient in ALG-1007 is effective in improving signs and symptoms of DED. ALG-1007 was well-tolerated with minimal instillation discomfort and no reported serious AEs.

scholarly journals Effectiveness and Optical Quality of Topical 3.0% Diquafosol versus 0.05% Cyclosporine A in Dry Eye Patients following Cataract Surgery

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jang Hoon Lee ◽  
In Seok Song ◽  
Kyoung Lae Kim ◽  
Sam Young Yoon
Keyword(s):  
Cataract Surgery ◽  
Dry Eye ◽  
Cyclosporine A ◽  
Ocular Surface ◽  
Ophthalmic Solution ◽  
Optical Quality ◽  
Ocular Surface Disease Index ◽  
Staining Score ◽  
Surface Staining

Purpose.To evaluate the effectiveness and optical quality of 3.0% topical diquafosol versus 0.05% cyclosporine A in dry eye patients following cataract surgery.Methods.In total, 40 eyes of 40 patients newly diagnosed with dry eye syndrome 1 week after cataract surgery were randomized to receive either 3.0% diquafosol ophthalmic solution six times daily or 0.05% cyclosporine A twice daily for 3 months. Outcome measures were tear film break-up time (TBUT), results on Schirmer 1 test, ocular surface staining score, the ocular surface disease index (OSDI) score, and higher-order aberrations (HOAs). Measurements were taken at baseline and at 1, 2, and 3 months.Results.In the diquafosol group, TBUT showed higher outcomes than the cyclosporine A group at 1 and 3 months. Both groups showed increased scores on Schirmer 1 test. The ocular surface staining score decreased in all periods in both groups. Vertical coma and total HOAs decreased more in the cyclosporine A group than in the diquafosol group at 3 months.Conclusion.Both 3.0% diquafosol and 0.05% cyclosporine A were effective in treating dry eye after cataract surgery. Diquafosol was more effective in increasing the tear secretion, but cyclosporine A was more effective in improving optical aberrations.

scholarly journals Diquafosol zur Behandlung der Keratokonjunktivitis sicca: 12-Monats-Ergebnisse einer prospektiven Studie

2021 ◽  
pp. 1-2
Author(s):  
Björn Bachmann
Keyword(s):  
Dry Eye ◽  
Real World ◽  
Tear Film ◽  
Ophthalmic Solution ◽  
Term Treatment ◽  
Summary Score ◽  
Open Label ◽  
Staining Score ◽  
Long Term Treatment

<b>Introduction:</b> Diquafosol is a P2Y<sub>2</sub> receptor agonist that has been shown to be effective in the treatment of dry eye disease (DED) in short-term studies; however, its long-term safety and effectiveness have not been evaluated in a real-world setting. <b>Methods:</b> This prospective, multicentre, open-label observational study was conducted in patients with DED over 12 months. Safety endpoints included the incidence of adverse drug reactions (ADRs) and serious ADRs. Effectiveness endpoints included change from baseline in keratoconjunctival staining score, tear film break-up time (BUT) and Dry Eye-related Quality of Life Score (DEQS). <b>Results:</b> A total of 580 patients were included, most of whom were female (82.9%). The proportion of patients who completed 12 months of observation was 55.0%, the most common reason for discontinuation was patient decision (54.6%). The incidence of ADRs was 10.7% and was highest during the first month of treatment (5.5%); no serious ADRs were reported. Compared with baseline, significant improvements in all effectiveness outcomes, including keratoconjunctival fluorescein staining score, BUT and DEQS summary score, were observed at each evaluation during the treatment period (p &#x3c; 0.001). <b>Conclusion:</b> The present, real-world study showed that diquafosol 3.0% ophthalmic solution was well tolerated and effective in the long-term treatment of DED.

scholarly journals Clinical effectiveness of diquafosol ophthalmic solution 3% in Korean patients with dry eye disease: a multicenter prospective observational study

2021 ◽  
Vol 14 (10) ◽  
pp. 1518-1526
Author(s):  
Youngsub Eom ◽  
Keyword(s):  
Dry Eye ◽  
Ophthalmic Solution ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Dependent Manner ◽  
Subjective Symptoms ◽  
Korean Patients ◽  
Staining Score ◽  
Switch Group ◽  
Diquafosol Ophthalmic Solution

AIM: To investigate the effectiveness of diquafosol ophthalmic solution 3% administered in Korean patients with dry eye disease in real-world clinical settings. METHODS: Diquafosol was administered for 8wk to 3 patient groups who received diquafosol as add-on therapy to existing medication (Add group, n=150); received diquafosol only (Monotherapy group, n=196); or discontinued part of their existing medication in favor of diquafosol (Switch group, n=11). Tear break-up time (TBUT), cornea and conjunctival staining based on National Eye Institute/Industry scoring scheme, subjective symptoms using the Ocular Surface Disease Index (OSDI) questionnaire, and meibum quality and expressibility were evaluated at baseline, week 4, and week 8. RESULTS: The mean TBUT increased (from 3.46, 3.92, and 5.84s, respectively, to 5.15, 5.53, and 8.59s, respectively) and corneal staining score decreased (from 2.23, 2.24, and 3.09, respectively, to 0.85, 0.97, and 1.64, respectively) in a time-dependent manner from baseline to week 8 in all three groups. Conjunctival staining score, OSDI questionnaire, and meibum quality and expressibility improved over time from baseline to week 8 in the Add and Monotherapy groups, but differences were not statistically significant in the Switch group. CONCLUSION: Diquafosol improves subjective symptoms and objective signs in patients treated with existing medicines combined with diquafosol and treated solely with diquafosol. Diquafosol can be used as an effective therapeutic agent for dry eye disease or additionally applied in patients who have insufficient response to existing medicines.

Sign in / Sign up

Export Citation Format

Share Document