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3D Cell Culture - A new approach to the study of dry eye disease research?

Dry and itchy eyes are annoying. That poking feeling like you’ve got sand in your eyes – the more you rub, the worse it gets. If this sounds familiar to you, you may have chronic dry eyes, and you’re in good company: Dry eyes disease (DED) is highly prevalent. A 2017 study on scope of dry eye disease found that more than 16 million people – including twice as many women as men – endure DED in the United States alone [1], causing an economic burden of over $55 billion.

These numbers highlight the importance of researching DED and developing effective therapies. In this article, we look at the opportunity provided by 3D cell culture to study DED and as an appropriate model for drug screening [2].


What is dry eye disease?

DED is caused by dysfunction or damage of the lacrimal gland (LG). One of the most common symptoms of dry eyes is blurred eyesight. Other common symptoms include stinging, burning, and scratching sensations in your eyes, red and watery eyes, sensitivity to light, filmy vision, difficulty wearing contact lenses, and a feeling of eye fatigue. Unfortunately, current therapies do not fully replenish the necessary lubrication to rescue optimal vision. People who suffer from DED today must rely on eye drops. The relief is wonderful, but short-lived.


What is the function of the lacrimal gland (LG)?

The lacrimal gland produces an ocular lubricating secretion to maximize the visual acuity and support homeostasis of the eye. Dysfunction of the LG can have numerous causes, including trauma, age-related degeneration, graft versus host disease, Sjögren’s syndrome, and chemotherapy secondary effects. These can all lead to LG morbidities such as ocular discomfort and DED.

Mild manifestations of DED can be partially tamed with artificial tears or anti-inflammatory drugs. However, these are only palliative management approaches that do not fully replenish the ocular lubrication and vision [2]. The eye drops also do not restore LG function and are therefore not sustainable in the mid-to-long-term since the biochemical composition of artificial tears is less complex and lacks similarities with the original tear composition.


How can the lacrimal gland be regenerated, and DED improved?

Fortunately, there are promising current biotechnologies for LG regeneration and improvement of DED. Researchers are experimenting with tissue engineering and regenerative medicine as an approach to permanently rescue LG function and reverse DED. Emerging in vitro and in vivo cell-based technologies are used for drug discovery in DED and for potential human transplantation techniques to regenerate LG tissues.


How can in vitro LG systems be modeled?

To better mimic human physiology, different animal models such as mice and pigs are used. When modeling the LG gland, pig models are closer to humans than mouse models. In cases where animal models are not useful, the advantages of magnetic 3D (M3D) cell culture as a tool for using primary human cells come into play.

Current promising therapies to restore LG secretion use the following approaches:

  • Stimulation of the remaining epithelial cells and stem cell niche
  • Transplantation of stem cells for gland homing, differentiation, and formation of new secretory units
  • Transplantation of ex vivo epithelial secretory cells or mini organs/organoids into the damaged glands

The latter approach has led to the development of organoid platforms that mimic the epithelial architecture and functional properties of the native LG organ [2].


Why is 3D cell culture an opportunity to study DED?

To date, results in new drug development for DED have been limited because in vitro models cannot mimic the biology of native LG well enough. Existing platforms for culturing LG organoids are scarce and not yet ready for consistent and scalable production for drug screening.

However, Magnetic 3D (M3D) Bioprinting is a novel system for 3D Biofabrication of cellular tissue in vitro using magnetic nanoparticles to bring cells together. M3D Cell Culture provides a scalable platform for consistent generation and handling of organoids.


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 [1] Farrand KF, Fridman M, Stillman IÖ, Schaumberg DA. Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older. Am J Ophthalmol. 2017 Oct;182:90-98. doi: 10.1016/j.ajo.2017.06.033. Epub 2017 Jul 10. PMID: 28705660.
[2] Rodboon T, Yodmuang S, Chaisuparat R, Ferreira JN. Development of high-throughput lacrimal gland organoid platforms for drug discovery in dry eye disease. SLAS Discov. 2022 Apr;27(3):151-158. doi: 10.1016/j.slasd.2021.11.002. Epub 2021 Dec 4. PMID: 35058190.

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