Advances in Functional Restoration of the Lacrimal Glands

Abstract

The lacrimal glands produce tears to support a healthy homeostatic environment on the ocular surface. The lacrimal gland dysfunction characteristic of dry eye disease causes ocular discomfort and visual disturbances and in severe cases can result in a loss of vision. The demand for adequate restoration of lacrimal gland function has been intensified due to advances in stem cell biology, developmental biology, and bioengineering technologies. In addition to conventional therapies, including artificial tears, tear alternatives (such as autologous serum eye drops) and salivary gland transplantation, a regenerative medicine approach has been identified as a novel strategy to restore the function of the lacrimal gland. Recent studies have demonstrated the potential of progenitor cell injection therapy to repair the tissue of the lacrimal glands. A current three-dimensional (3D) tissue engineering technique has been shown to regenerate a secretory gland structure by reproducing reciprocal epithelial-mesenchymal interactions during ontogenesis in vitro and in vivo. A novel direct reprogramming method has suggested a possibility to induce markers in the lacrimal gland developmental process from human pluripotent stem cells. The development of this method is supported by advances in our understanding of gene expression and regulatory networks involved in the development and differentiation of the lacrimal glands. Engineering science has proposed a medical device to stimulate tearing and a bio-hybrid scaffold to reconstruct the 3D lacrimal gland structure. In this review, we will summarize recent bioengineering advances in lacrimal gland regeneration toward the functional restoration of the lacrimal glands as a future dry eye therapy.

Morphological and functional relationship between the orbital gland and olfaction in Upupa epops (hoopoe) and Bubulcus ibis (cattle egret)

“…The lacrimal and Harderian gland play an essential role in eye health. The lacrimal gland in mammals, particularly in humans, has been the focus of extensive research, with clinical trials attempting to develop several numerous innovative products for the functional restoration of the lacrimal gland as a potential dry eye therapy (Hirayama, 2018; Butovich et al, 2021). However, in other vertebrates such as birds, the lacrimal gland has not received sufficient attention as evident from the current ornithology literature.…”

Serum drops—the last resort for topical treatment after refractive surgery and laser in situ keratomileusis-induced neuropathic epitheliopathy (LINE)

“…Autologous serum drops are proven therapy for moderate to severe dry eye. In many countries they are unlicensed medication and they are subject of special regulations (16,17). Most of the learned ophthalmology societies in Europe are having special guidelines for preparation and application of such products (18).…”

Salivary Gland Transplantation as a Promising Approach for Tear Film Restoration in Severe Dry Eye Disease

“…A tissue-engineered lacrimal gland may be potentially used as an exocrine tissue for patients whose lacrimal gland is entirely nonfunctional. An attempt has been made to reconstruct the lacrimal gland by the induction of whole organs using special cell populations and a 'scaffold' for cells to grow on [63][64][65][66][67][68][69]. Cell populations, including lacrimal gland stem cells [70] and epithelial cells [69], have demonstrated the possibility of constructing a lacrimal gland functional unit in vitro.…”