Looking into the Eyes—In Vitro Models for Ocular Research

Lieto, Krystyna; Skopek, Rafał; Lewicka, Aneta; Stelmasiak, Marta; Klimaszewska, Emilia; Zelent, Arthur; Szymański, Łukasz; Lewicki, Sławomir

doi:10.3390/ijms23169158

Cited by 18 publications

(13 citation statements)

References 102 publications

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“…The unique anatomical structures of the eye represent multiple barriers, which modify drug absorption [168]. This and the different fluid dynamics make this organ an especially hard-to-simulate environment to develop in vitro, ex vivo, or cell culture techniques for bioavailability testing [169]. No true, validated method is available for the replacement of the in vivo Draize rabbit eye test, which is the gold standard for not only bioavailability but also toxicity testing due to its high similarity and ease to use compared to other mammalian models [170].…”

Section: In Vitromentioning

confidence: 99%

“…In general, they are cheap, easy to maintain, and reproducible ways to carry out drug transport experiments. Meanwhile, the modern but complicated in vitro 3D cell culture methods, such as the reconstructed human tissue assays SkinEthic™ Human Corneal Epithelium and EpiOcular Eye Irritation test, are rarely utilized by current researchers due to their high price, low repeatability, and limited transition towards in vivo results [169,180,181]. Apart from these, 2D cell cultures of immortalized cell lines such as ARPE-19 or TERT-RPE are mainly used to screen cytotoxicity before in vivo tests.…”

Section: Cell Culturementioning

confidence: 99%

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Recent Options and Techniques to Assess Improved Bioavailability: In Vitro and Ex Vivo Methods

et al. 2023

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Bioavailability assessment in the development phase of a drug product is vital to reveal the disadvantageous properties of the substance and the possible technological interventions. However, in vivo pharmacokinetic studies provide strong evidence for drug approval applications. Human and animal studies must be designed on the basis of preliminary biorelevant experiments in vitro and ex vivo. In this article, the authors have reviewed the recent methods and techniques from the last decade that are in use for assessing the bioavailability of drug molecules and the effects of technological modifications and drug delivery systems. Four main administration routes were selected: oral, transdermal, ocular, and nasal or inhalation. Three levels of methodologies were screened for each category: in vitro techniques with artificial membranes; cell culture, including monocultures and co-cultures; and finally, experiments where tissue or organ samples were used. Reproducibility, predictability, and level of acceptance by the regulatory organizations are summarized for the readers.

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Section: In Vitromentioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

Recent Options and Techniques to Assess Improved Bioavailability: In Vitro and Ex Vivo Methods

et al. 2023

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“…Spherical cellular aggregates, such as spheroids, derived from primary tissue and composed of a single cell type, improve 2D cultures by creating a 3D environment with greater cell–cell interactions. Consequently, cell behavior in response to therapeutic treatments resembles that of native tissue more closely. − It can take up to a month for mature corneal spheres to form, with differentiation times varying greatly between studies and being related to the type of cell used for spheroid development . Spheroids, notable larger spheres composed of various stages of cells, are commonly used in oncology because they represent small solid tumors. , These large spheres are the result of limited nutrition transport, hypoxia, and waste accumulation in the interior regions of large spheroids, which may influence cell behavior .…”

Section: In Vitro Reconstructed Corneal Tissue Models To Study Drug P...mentioning

confidence: 99%

“…Consequently, cell behavior in response to therapeutic treatments resembles that of native tissue more closely. − It can take up to a month for mature corneal spheres to form, with differentiation times varying greatly between studies and being related to the type of cell used for spheroid development . Spheroids, notable larger spheres composed of various stages of cells, are commonly used in oncology because they represent small solid tumors. , These large spheres are the result of limited nutrition transport, hypoxia, and waste accumulation in the interior regions of large spheroids, which may influence cell behavior . In addition, they can be used to investigate drug absorption, drug response, and cell–cell interactions, amongst others.…”

Section: In Vitro Reconstructed Corneal Tissue Models To Study Drug P...mentioning

confidence: 99%

In Vitro and Ex Vivo Models for Assessing Drug Permeation across the Cornea

et al. 2023

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Drug permeation across the cornea remains a major challenge due to its unique and complex anatomy and physiology. Static barriers such as the different layers of the cornea, as well as dynamic aspects such as the constant renewal of the tear film and the presence of the mucin layer together with efflux pumps, all present unique challenges for effective ophthalmic drug delivery. To overcome some of the current ophthalmic drug limitations, the identification and testing of novel drug formulations such as liposomes, nanoemulsions, and nanoparticles began to be considered and widely explored. In the early stages of corneal drug development reliable in vitro and ex vivo alternatives, are required, to be in line with the principles of the 3Rs (Replacement, Reduction, and Refinement), with such methods being in addition faster and more ethical alternatives to in vivo studies. The ocular field remains limited to a handful of predictive models for ophthalmic drug permeation. In vitro cell culture models are increasingly used when it comes to transcorneal permeation studies. Ex vivo models using excised animal tissue such as porcine eyes are the model of choice to study corneal permeation and promising advancements have been reported over the years. Interspecies characteristics must be considered in detail when using such models. This review updates the current knowledge about in vitro and ex vivo corneal permeability models and evaluates their advantages and limitations.

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“…These animal-based models raised much public concern given the potential for the animals to feel pain for days on end during testing of a hazardous substance. Routine cosmetic testing has become increasingly undesirable as public awareness of animal welfare issues has grown, leading manufacturers to seek out types of testing that are more humane and less expensive [ 10 , 11 ].…”

Section: Assessments Of Ocular Toxicitymentioning

confidence: 99%

Toxic External Exposure Leading to Ocular Surface Injury

Rauchman

Locke

Albert

et al. 2023

Vision

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The surface of the eye is directly exposed to the external environment, protected only by a thin tear film, and may therefore be damaged by contact with ambient particulate matter, liquids, aerosols, or vapors. In the workplace or home, the eye is subject to accidental or incidental exposure to cleaning products and pesticides. Organic matter may enter the eye and cause infection. Ocular surface damage can trigger a range of symptoms such as itch, discharge, hyperemia, photophobia, blurred vision, and foreign body sensation. Toxin exposure can be assessed clinically in multiple ways, including via measurement of tear production, slit-lamp examination, corneal staining, and conjunctival staining. At the cellular level, environmental toxins can cause oxidative damage, apoptosis of corneal and conjunctival cells, cell senescence, and impaired motility. Outcomes range from transient and reversible with complete healing to severe and sight-compromising structural changes. Classically, evaluation of tolerance and safety was carried out using live animal testing; however, new in vitro and computer-based, in silico modes are superseding the gold standard Draize test. This review examines how environmental features such as pollutants, temperature, and seasonality affect the ocular surface. Chemical burns to the eye are considered, and approaches to protect the ocular surface are detailed.

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Looking into the Eyes—In Vitro Models for Ocular Research

Cited by 18 publications

References 102 publications

Recent Options and Techniques to Assess Improved Bioavailability: In Vitro and Ex Vivo Methods

Recent Options and Techniques to Assess Improved Bioavailability: In Vitro and Ex Vivo Methods

In Vitro and Ex Vivo Models for Assessing Drug Permeation across the Cornea

Toxic External Exposure Leading to Ocular Surface Injury

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