Influences of Methylcellulose on Corneal Epithelial Wound Healing

Lin, Chang‐Ping; Boehnke, Matthias

doi:10.1089/jop.1999.15.59

Cited by 17 publications

(13 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such in vitro models are already being employed in some medical fields [15][16][17] and have been suggested for pharmacological testing of ocular drugs [18][19][20][21][22]. Long-term use of topical antiglaucomatous drugs has been shown to induce ocular surface inflammation [23] and fibrosis [24].…”

Section: Discussionmentioning

confidence: 99%

In vitro Toxicity of Rivastigmine and Donepezil in Cells of Epithelial Origin

Goldblum¹,

Gygax²,

Böhnke³

et al. 2002

Ophthalmic Res

View full text Add to dashboard Cite

Neurospecific acetylcholinesterase inhibitors have been shown to lower intraocular pressure (IOP) in normal rabbits and might have additional neuroprotective effects. This study was set out to explore and compare the toxicity of two selective acetylcholinesterase inhibitors, rivastigmine and donepezil, on two standardized cell lines of epithelial origin. Chang and Vero cells were incubated with various concentrations of rivastigmine or donepezil. Acute toxicity (4 h) was assessed by monitoring the permeability of cells to propidium iodide. Chronic toxicity (7 days) was determined by monitoring the effect of the two drugs on esterase activity and cell proliferation. The viability of cells was also assessed morphologically by microscopic inspection. Signs of acute toxicity became manifest at a rivastigmine concentration of 50 mg/ml in both Chang and Vero cells. Indications of chronic toxicity became obvious at concentrations of as low as 1 × 10^–5 mg/ml. In contrast, degenerative morphological changes became manifest only at a concentration of as high as 1 mg/ml. In donepezil-treated cells, acute toxicity was not observed in the concentration range tested, whereas chronic toxicity was detected at 1 × 10^–1 mg/ml in both Chang and Vero cells, a concentration at which degenerative morphological changes became evident as well. In contrast to rivastigmine, donepezil elicited no signs of acute or chronic toxicity in either Chang or Vero cells at the IOP-lowering concentration of 1 × 10^–4 mg/ml. At this dose, the drug is therefore unlikely to evoke deleterious effects on ocular surface tissues in the clinical setting.

show abstract

Section: Discussionmentioning

confidence: 99%

In vitro Toxicity of Rivastigmine and Donepezil in Cells of Epithelial Origin

Goldblum¹,

Gygax²,

Böhnke³

et al. 2002

Ophthalmic Res

View full text Add to dashboard Cite

show abstract

“…Hence, the search for new drugs that stabilize the corneal epithelium has been, and still is, intensive. [3][4][5][6][7] Before being approved by federal law for clinical use in humans, candidate drugs are subjected to a series of tests to assess both their impact on wound healing and their toxicity.…”

Section: Introductionmentioning

confidence: 99%

An Ex-Vivo, Whole-Globe Porcine Model of Corneoepithelial Wound Healing Tested Using Immunomodulatory Drugs

Flueckiger

Kodjikian²,

Halberstadt³

et al. 2005

Journal of Ocular Pharmacology and Therapeutics

Self Cite

View full text Add to dashboard Cite

Drug screening with this ex vivo porcine model permits a reproducibly quantitative and time- and dose-dependent assessment of corneoepithelial wound healing. This model corresponds more closely to the clinical situation than cell culturing and may, therefore, be useful in evaluating novel pharmaceutical agents, thereby helping to cut down on the number of animal experiments performed prior to the instigation of clinical trials.

show abstract

“…MC solutions are also stable over the pH range that is well tolerated by the eye, and its effectiveness in solutions to treat dry eye, punctate keratitis and epithelial defects has been reported. 25) In this study, we attempted to enhance the delaying effect of DSF eye drops on cataract development by using low-substituted MC. The anti-cataract effect of the drops was evaluated by a kinetic parameter analyzed from the lens opacification vs. age-profile curves using a one-exponential equation.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Evaluation of the Anti-cataract Effect of Eye Drops Containing Disulfiram and Low-Substituted Methylcellulose Using ICR/f Rats as a Hereditary Cataract Model

Nagai

Ito

Takeuchi

2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

We attempted to develop anti-cataract eye drops using disulfiram (DSF) and low-substituted methylcellulose (MC), and evaluated their anti-cataract effect in terms of the lens opacification vs. age-profile curves using a one-exponential equation. The eye drops were prepared using 0.5% DSF and 2% MC (DSF eye drops), and ICR/f rats, a recessive-type hereditary cataractous strain, were used as the experimental model. Gelation of DSF eye drops containing MC was first observed at about 35°C, close to body temperature. In in vivo transcorneal penetration experiments using rabbit corneas, only diethyldithiocarbamate (DDC) was detected in the aqueous humor, while DSF was not detected. The DDC penetration level of DSF eye drops containing MC was approximately 1.3-fold higher than that of DSF eye drops. The opacification rate constant (k) of ICR/f rat instilled with DSF eye drops with or without MC was lower, and the initial time of opacification (τ) was longer than those of ICR/f rats instilled with saline. Furthermore, the k of ICR/f rats instilled with DSF eye drops with MC was lower than that of ICR/f rats instilled with DSF eye drops without MC. In conclusion, the analysis of kinetic parameters including k and τ using a one-exponential equation provided useful information for clarifying the anti-cataract effect of eye drops. ICR/f rats instilled with DSF eye drops using a low-substituted MC-based drug delivery system demonstrated a delay in cataract development, probably resulting from an increase in the retention of DSF eye drops on the cornea. Key words cataract; disulfiram; methylcellulose; 2-hydroxypropyl-β-cyclodextrin; ICR/f rat A cataract is defined as any alteration in the optical homogeneity of the lens or decrease in its transparency, 1,2) and numerous factors have been implicated in the etiology of cataracts including genetic factors, diabetes, smoking, nutrition, the cumulative effect of X-rays, UV irradiation, and alterations in both endocrine and enzymatic equilibria.2-7) In human senile cataracts, an ionic imbalance in the lens with increased levels of Ca 2+ is related to cataract development. ; however, no potent anti-cataract drugs have yet to be introduced due to uncertainties regarding efficacy and safety.Disulfiram (DSF), a dimer of diethyldithiocarbamate (DDC), has long been used to treat alcoholic syndrome without severe side effects.11) DSF is a powerful antioxidant that scavenges reactive oxygen species including hydroxyl radicals, superoxide, and peroxynitrite, and chelates metal ions in rats.12,13) However, its application in the ophthalmic field is limited due to its poor water solubility. One problem with lipophilic drugs, such as DSF, administered as aqueous eye drops is obtaining the desired drug concentration in any drug delivery system. Cyclodextrins are cyclic oligosaccharides comprising R-D-glucose linked by R-(1-4) glucosidic bonds. The potential use of natural cyclodextrins and their synthetic derivatives has been studied extensively to improve certain properties such as their solub...

show abstract

Influences of Methylcellulose on Corneal Epithelial Wound Healing

Cited by 17 publications

References 10 publications

In vitro Toxicity of Rivastigmine and Donepezil in Cells of Epithelial Origin

In vitro Toxicity of Rivastigmine and Donepezil in Cells of Epithelial Origin

An Ex-Vivo, Whole-Globe Porcine Model of Corneoepithelial Wound Healing Tested Using Immunomodulatory Drugs

Pharmacokinetic and Pharmacodynamic Evaluation of the Anti-cataract Effect of Eye Drops Containing Disulfiram and Low-Substituted Methylcellulose Using ICR/f Rats as a Hereditary Cataract Model

Contact Info

Product

Resources

About