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Masatoshi Hirayama, Miho Ogawa, Masamitsu Oshima, Tetsuya Kawakita, Shigeto Shimmura, Takashi Tsuji, Kazuo Tsubota; Fully Functional Bioengineered Lacrimal Gland Regeneration as an Organ Replacement Regenerative Therapy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2189.
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© ARVO (1962-2015); The Authors (2016-present)
Tear secreted from lacrimal gland plays a multifaceted role to maintain a homeostatic microenvironment for ocular surface. Dry eye is an important public health problem, and it is expected to develop a novel therapeutic treatment for the restoration of the lacrimal gland functions. Here, we report a successful fully functioning lacrimal gland replacement achieved though the transplantation of bioengineered lacrimal gland germ in adult mouse.
The care and handling of animals were performed in accordance with NIH guidelines. Protocols were approved by the Animal Care and Use Committee. We had successfully demonstrated the bioengineered lacrimal gland germ regeneration by organ germ method (ARVO2012). We regenerated the bioengineered lacrimal gland germ and harderian gland germ, and transplanted them to adult lacrimal gland defect model mouse. The development of bioengineered glands, histological structure including expression of aquapolin-5 (AQP5), lactoferrin and lipids, tear secretion ability and ocular surface protection effect were analyzed.
The bioengineered lacrimal gland germ and harderian gland germ successfully achieved correct gland structure including acini, myoepithelial cells and nerve, followed by successful duct integration. AQP5 and lactoferrin in the bioengineered lacrimal gland, and lipids in the bioengineered harderian gland were histologically detected. The bioengineered lacrimal gland received appropriate neural control and had a secretion ability equivalent to that of natural lacrimal gland. Tear from the bioengineered glands had appropriate tear components such as lactoferrin. The ocular surface status including fluorescein staining and corneal epithelial thickness was significantly improved in the bioengineered lacrimal gland transplantation mouse compared with that in the lacrimal gland defect model mouse.
We demonstrated that bioengineered lacrimal gland and harderian gland, which had the correct gland structure, could produce the tear followed by successful duct integration and restore the lacrimal gland physiological functions in response to nervous stimulations, and could protect the ocular surface. This study thus represents a substantial advance and demonstrates the possibility of novel therapeutic approach for dry eye as a future organ replacement regenerative therapy.
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