In vitro effects of sex hormones in human meibomian gland epithelial cells

Schröder, Antje; Abrar, D; Hampel, Ulrike; Schicht, Martin; Paulsen, Friedrich; Garreis, Fabian

doi:10.1016/j.exer.2016.08.009

Cited by 35 publications

(22 citation statements)

References 53 publications

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“…Importantly, no similarities between human meibomian lipidome and lipidome of immortalized HMGEC were found in an independent study conducted using the same line of immortalized HMGEC, either (Hampel et al, 2015). Moreover, no effects of stimulation of HMGEC with sex hormones on the lipid production or cell morphology and proliferation have been found (Schroder et al, 2016). In the latter publication, the authors concluded that the immortalized HMGEC "do not reflect the biology of meibomian gland epithelial cells in vivo exactly".…”

Section: A Concept Of Meibogenesismentioning

confidence: 99%

Meibomian glands, meibum, and meibogenesis

Butovich

2017

Experimental Eye Research

113

118

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Meibum is a lipid-rich secretion that is produced by fully differentiated meibocytes in the holocrine Meibomian glands (MG) of humans and most mammals. The secretion is a part of a defense mechanism that protects the ocular surface from hazardous environmental factors, and from desiccation. Meibomian lipids that have been identified in meibum are very diverse and unique in nature. The lipid composition of meibum is different from virtually any other lipid pool found in the human body. In fact, meibum is quite different from sebum, which is the closest secretion that is produced by anatomically, physiologically, and biochemically related sebaceous glands. However, meibum of mice have been shown to closely resemble that of humans, implying similar biosynthetic mechanisms in MG of both species. By analyzing available genomic, immunohistochemical, and lipidomic data, we have envisioned a unifying network of enzymatic reactions that are responsible for biosynthesis of meibum, which we call meibogenesis. Our current theory is based on an assumption that most of the biosynthetic reactions of meibogenesis are catalyzed by known enzymes. However, the main features that make meibum unique – the ratio of identified classes of lipids, the extreme length of its components, extensive ω-hydroxylation of fatty acids and alcohols, iso- and anteiso-branching of meibomian lipids (e.g. waxes), and the presence of rather unique complex lipids with several ester bonds – make it possible that either the activity of known enzymes is altered in MG, or some unknown enzymes contribute to the processes of meibogenesis, or both. Studies are in progress to elucidate meibogenesis on molecular level.

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Section: A Concept Of Meibogenesismentioning

confidence: 99%

Meibomian glands, meibum, and meibogenesis

Butovich

2017

Experimental Eye Research

113

118

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“…iHMGEC cultured in serum-free medium were compared with those cultured in serum-containing medium. Both oestradiol and DHT increased gene expression for keratinisation in serum-free medium and, interestingly, DHT also downregulated gene expression of lipid synthesis enzymes 47. These findings contrast with the positive effects of androgens on iHMGEC, found by Khandelwal58 and in mice studies 55–57.…”

Section: Significance Of Intracrinologymentioning

confidence: 68%

“…This study used 1 nM 17β-oestradiol and 10 nM DHT to modulate gene expression of meibomian gland dysfunction-associated markers in iHMGEC 47. iHMGEC cultured in serum-free medium were compared with those cultured in serum-containing medium.…”

Section: Significance Of Intracrinologymentioning

confidence: 99%

Local synthesis of sex hormones: are there consequences for the ocular surface and dry eye?

et al. 2017

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Sex hormones are associated with the physiology and pathophysiology of almost all organs in the body, as well as most diseases. Interest in the associations between sex hormones and ocular tissues has increased in recent years. Androgens may have a positive effect on dry eye, whereas the effects of oestrogen on ocular conditions remain unclear. Intracrinology, the local synthesis and metabolism of hormones that is unique to humans, is of relevance to the eye and may help to explain why studies of the relationship between oestrogens and dry eye signs and symptoms are inconclusive. Knowledge of the pathways of hormone formation and metabolism is crucial to understanding the pathogenesis of ocular disease including dry eye. This review examines the mechanisms of steroidal sex hormone biosynthesis and reviews the significance of locally produced sex hormones, with a focus on ocular surface tissues. Much of the current literature is based on animal studies, which may not be transferable to humans due to the absence of intracrine production in animals. A large proportion of the human studies investigate systemic hormone levels rather than local levels. There is subsequently a need for additional studies to provide a better understanding of the local production of sex hormones within the human eye and ocular surface and to clarify the relationships between ocular levels of sex hormones and conditions including dry eye.

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“…Our results support previous reports of HMGECs being unable to differentiate to an advanced state. 15,23 This is most probably due to the fact that the cells are derived from an immortalized cell line that is subjected to a cell cycle program very different from the physiological situation. Since meibocyte apoptosis is considered a key factor involved in the mechanisms of hypermaturation and becoming meibum, the immortalization itself may represent an inherent obstacle for those cells on their way toward an advanced differentiation status.…”

Section: Discussionmentioning

confidence: 99%

“…14 Previous studies, including some from our group, showed the functional influence of cultivation conditions, 15,16 neurotransmitters, 17,18 growth factors, 19,20 x-3 fatty acids, 21 sex hormones, 22,23 and pharmacologic substances 24 on HMGEC. However, all of these studies rely on 2D cell culture conditions or limited animal experiments.…”

mentioning

confidence: 99%

Differentiation Patterns of Immortalized Human Meibomian Gland Epithelial Cells in Three-Dimensional Culture

Asano

Hampel

Garreis

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To establish a simplified three-dimensional (3D) meibomian gland culture model using a meibomian gland epithelial cell (HMGEC) line that might be a useful tool to gain deeper insights into meibomian gland dysfunction. For this purpose, 3D differentiation patterns and growth characteristics of HMGECs were studied on various membranes/scaffolds as well as in hanging drops.METHODS. Several types of inserts consisting of different materials (Millicell-HA, Millicell-PCF, ThinCert, and Alvetex) as well as hanging drop culture were analyzed. Culture conditions were optimized employing exposure to air (air-lift) and different cell culture media for a maximum of 28 days. To characterize cell differentiation in the developed 3D model, the expression pattern of cytokeratins was investigated by immunohistochemistry. Sudan III staining was performed for detection of lipid formation and transmission electron microscopy (TEM) was used for ultrastructural analysis. RESULTS.Only Alvetex scaffolds and the hanging drop method revealed satisfactory results with regard to 3D culture. Continuous use of proliferation medium (serum-free keratinocyte medium containing epidermal growth factor and bovine pituitary extract) and air-lift were important steps for HMGEC differentiation in 3D culture. However, HMGECs only reached a differentiating state and never became mature or hypermature. When cultured in hanging drops, HMGECs showed serum-induced keratinization processes. CONCLUSIONS.HMGECs have the capability to differentiate in a long-term 3D culture, especially when adapted to an air-rich environment. However, even in the 3D format, HMGECs only reach a state of differentiating meibocytes.

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In vitro effects of sex hormones in human meibomian gland epithelial cells

Cited by 35 publications

References 53 publications

Meibomian glands, meibum, and meibogenesis

Meibomian glands, meibum, and meibogenesis

Local synthesis of sex hormones: are there consequences for the ocular surface and dry eye?

Differentiation Patterns of Immortalized Human Meibomian Gland Epithelial Cells in Three-Dimensional Culture

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