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Corneal Tissue Engineering: An In Vitro Model of the Stromal-nerve Interactions of the Human Cornea
Published on: January 24, 2018
Human Corneal Tissue Model for Nociceptive Assessments
Wang Siran1, Chiara E Ghezzi1, Dana M Cairns1
1Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA, 02155, USA.
Abstract:
New in vitro tissue models to mimic in vivo conditions are needed to provide insight into mechanisms involved in peripheral pain responses, potential therapeutic strategies to address these responses, and to replace animal models for such indications. For example, the rabbit cornea Draize test has become the standard method used for decades to screen ophthalmic drug and consumer product toxicity. In vitro tissue models with functional innervation have the potential to replace in vivo animal testing and provide sophisticated bench tools to study ocular nociception and its amelioration. Herein, full thickness, innervated, 3D human corneal tissues are grown under physiologically relevant culture conditions to study nociceptive-related responses, by mimicking ocular environmental cues, including intraocular pressure (IOP) and tear flow (TF). Capsaicin, a chili pepper-derived irritant known to cause a burning sensation in mammalian tissues is utilized as a nociceptive stimulant to induce pain, while subsequent serum treatment is used to mimic healing. Pain mediators released upon capsaicin stimulation and cell regrowth after serum treatment are characterized to assess ocular responses in this new, innervated, human corneal tissue system for comparison of outcomes to established animal and related responses.
Insights
Researchers developed a novel 3D human corneal tissue model to study eye pain and healing. This innovative in vitro system aims to replace animal testing for ophthalmic drug development and toxicity screening.
Area of Science:
- Ophthalmology
- Tissue Engineering
- Neuroscience
Background:
- In vitro models are crucial for understanding peripheral pain mechanisms and developing therapeutics.
- Current methods for assessing ocular toxicity, like the rabbit cornea Draize test, rely on animal models.
- Innervated in vitro tissue models offer a promising alternative to animal testing for studying ocular nociception.
Purpose of the Study:
- To develop and characterize a novel 3D human corneal tissue model with functional innervation.
- To mimic physiological ocular conditions, including intraocular pressure (IOP) and tear flow (TF).
- To assess nociceptive responses and healing mechanisms in an ocular tissue model.
Main Methods:
- Cultured full-thickness, 3D human corneal tissues under physiologically relevant conditions.
- Utilized capsaicin as a nociceptive stimulant to induce pain responses.
- Applied serum treatment to simulate wound healing and characterized released pain mediators and cell regrowth.
Main Results:
- Successfully developed an innervated 3D human corneal tissue model.
- Demonstrated the model's ability to respond to nociceptive stimuli (capsaicin) and simulate healing (serum treatment).
- Characterized pain mediators and cellular responses, providing a basis for comparison with in vivo data.
Conclusions:
- The developed 3D human corneal tissue model represents a significant advancement in in vitro ocular research.
- This model can provide insights into ocular nociception and therapeutic interventions.
- It holds potential for replacing animal testing in ophthalmic drug and consumer product safety evaluations.
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