137the lacrimal glands has been required to redeem biological tear fluids (Hirayama
et al. 2015 ).
This review summarized the physiological functions, development of the lacri-
mal glands, and attempts to restore functions of the lacrimal glands from published
research. We detailed that there is potential for a novel, fully functional lacrimal
gland regeneration as a next-generation regenerative medicine.
8.2 Physiological Function of Tears from the Lacrimal
Glands
Tear secretion from the lacrimal glands is a critical factor for function and homeo-
static microenvironment of the ocular surface (Mishima 1965 ; Lemp 1973 ). The
lacrimal gland consists of the main lacrimal gland, which produces most of aqueous
tears, and small accessory lacrimal glands (Schechter et al. 2010 ). The histological
structure of mature lacrimal glands is constructed by an organized tubuloalveolar
system with the acini, the ducts that are a pathway of fluid from the acini to a muco-
sal surface, and the myoepithelial cells that wrap the acini and early duct elements
(Schechter et al. 2010 ). A tear film consisting of triple layers of lipid, aqueous, and
mucin contributes to the ocular surface wetness, lid lubrication, and optical proper-
ties of the ocular surface (Lemp 1987 ; Yokoi et al. 2014 ). The tear aqueous layer is
formed by secretion from the lacrimal glands and contains water and many tear
proteins, including lactoferrin, for expression of biological functions such as mois-
turizing the ocular surface and antimicrobial activity (Hirayama et al. 2013b; Ohashi
et al. 2006 ). The lacrimal gland and tear functions are essential for healthy ocular
surface in protecting the ocular epithelium and visual function.
8.3 Organogenesis of the Lacrimal Glands
The lacrimal glands are anatomically classified as serous secretory glands, which
are constituted of various cell types including acini, acini-enveloping myoepithelial
cells, duct, and peripheral interstitial tissues including nerves (Schechter et al.
2010 ). This reasonable 3D histo-architecture for tear secretion is organized by a
reciprocal epithelial and mesenchymal interaction during organogenesis process in
embryonic stage, which is a developmental system commonly observed in other
ectodermal organs such as teeth, hair follicle, and salivary glands (Takahashi et al.
1998 ; Makarenkova et al. 2000 ; Pispa and Thesleff 2003 ; Thesleff 2003 ; Tucker
et al. 2004 ; Sharpe and Young 2005 ). After the induction of initial epithelial bud of
the lacrimal gland on ocular surface epithelium, the lacrimal gland germ shows
branching morphogenesis with stalk elongation and cleft formation (Kammandel
et al. 1999 ). In murine, the lacrimal gland’s bud occurs on embryonic day (ED) 13.5
8 Functional Lacrimal Gland Regeneration