In Vitro Assessment of the Cytotoxicity of Anti-allergic Eye Drops Using 5 Cultured Corneal and Conjunctival Cell Lines

Ayaki, Masahiko; Iwasawa, Atsuo; Yaguchi, Shigeo; Koide, Ryohei

doi:10.5650/jos.60.139

Cited by 14 publications

(18 citation statements)

References 18 publications

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“…However, dilution of these formulations up to 100 times diminished the cytotoxicity substantially suggesting that the endothelial toxicity risk in vivo is small. Toxicity results of ophthalmic solutions suggest that the survival rates of primary corneal endothelial cells are in general comparable to those of bovine and rabbit corneal epithelial and SIRC cell lines, but the rank-order is compound dependent [137, 141]. …”

Section: Toxicity Tests With Corneal Cell Culture Modelsmentioning

confidence: 99%

Human corneal cell culture models for drug toxicity studies

Rönkkö

Vellonen

Järvinen

et al. 2016

Drug Deliv. and Transl. Res.

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In vivo toxicity and absorption studies of topical ocular drugs are problematic, because these studies involve invasive tissue sampling and toxic effects in animal models. Therefore, different human corneal models ranging from simple monolayer cultures to three-dimensional models have been developed for toxicological prediction with in vitro models. Each system has its own set of advantages and disadvantages. Use of non-corneal cells, inadequate characterization of gene-expression profiles, and accumulation of genomic aberrations in human corneal models are typical drawbacks that decrease their reliability and predictive power. In the future, further improvements are needed for verifying comparable expression profiles and cellular properties of human corneal models with their in vivo counterparts. A rapidly expanding stem cell technology combined with tissue engineering may give future opportunities to develop new tools in drug toxicity studies. One approach may be the production of artificial miniature corneas. In addition, there is also a need to use large-scale profiling approaches such as genomics, transcriptomics, proteomics, and metabolomics for understanding of the ocular toxicity.

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Section: Toxicity Tests With Corneal Cell Culture Modelsmentioning

confidence: 99%

Human corneal cell culture models for drug toxicity studies

Rönkkö

Vellonen

Järvinen

et al. 2016

Drug Deliv. and Transl. Res.

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“…However, in recent years plenty of evidence has shown that they are not the only players of the inflammatory cascade triggered at the ocular surface by chronic topical therapies. The medical compounds themselves may induce ocular damage in predisposed patients in a cumulative effect related to dosage and duration of therapy or preexisting diseases (Table 2) [14,21,[71][72][73][74][75][76][77][78][79][80][81][82]. Therefore, although the advent of preservative-free topical ophthalmic compounds has certainly represented a significant innovation in ophthalmic drug development, the use of preserved eye drops does not need to be banned a priori.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, it has been described with both in-vitro, in-vivo, and clinical studies that the different antiallergic eye drops have different toxic effects on the ocular surface [20]. For instance, in a recent study [21] Ocular surface damage by ophthalmic compounds Mantelli et al 465 Key points A red eye is a common finding in patients under chronic eye drop treatment. Adverse reactions to eye drop treatments can be induced by both preservatives and active compounds in predisposed patients.…”

Section: Allergic Reactionsmentioning

confidence: 96%

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Ocular surface damage by ophthalmic compounds

Mantelli

Tranchina

Lambìase

et al. 2011

Current Opinion in Allergy &Amp; Clinical Immunology

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“…BAC causes surface-active molecules to bind to cellular epithelium and rapidly intercalate into the bilaminar membrane, and thus, BAC can disrupt the precorneal tear film and damage the ocular surface [14151617]. The BAC concentration range in topical ocular solutions typically ranges between 0.004% and 0.025% [18], that is, up to 25 times higher than its lowest concentration.…”

Section: Discussionmentioning

confidence: 99%

Comparison of cytotoxicities and wound healing effects of diquafosol tetrasodium and hyaluronic acid on human corneal epithelial cells

Lee

Kim

et al. 2017

Korean J Physiol Pharmacol

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This study aimed to compare the cellular toxicities of three clinically used dry eye treatments; 3% diquafosol tetrasodium and hyaluronic acid at 0.3 and 0.18%. A methyl thiazolyltetrazoiun (MTT)-based calorimetric assay was used to assess cellular proliferation and a lactate dehydrogenase (LDH) leakage assay to assess cytotoxicity, using Human corneal epithelial cells (HCECs) exposed to 3% diquafosol tetrasodium, 0.3% hyaluronic acid (HA), or 0.18% HA or 1, 6 or 24 h. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy, and wound widths were measured 24 h after confluent HCECs were scratched. Diquafosol had a significant, time-dependent, inhibitory effect on HCEC proliferation and cytotoxicity. HCECs treated with diquafosol detached more from the bottoms of dishes and damaged cells showed degenerative changes, such as, reduced numbers of microvilli, vacuole formation, and chromatin of the nuclear remnant condensed along the nuclear periphery. All significantly stimulated reepithelialization of HCECs scratched, which were less observed in diquafosol. Therefore, epithelial toxicity should be considered after long-term usage of diquafosol and in overdose cases, especially in dry eye patients with pre-existing punctated epithelial erosion.

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In Vitro Assessment of the Cytotoxicity of Anti-allergic Eye Drops Using 5 Cultured Corneal and Conjunctival Cell Lines

Cited by 14 publications

References 18 publications

Human corneal cell culture models for drug toxicity studies

Human corneal cell culture models for drug toxicity studies

Ocular surface damage by ophthalmic compounds

Comparison of cytotoxicities and wound healing effects of diquafosol tetrasodium and hyaluronic acid on human corneal epithelial cells

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