Monomeric serum immunoglobulin A (IgA) can contribute to the development of various autoimmune diseases, but the regulation of serum IgA effector functions is not well defined. Here, we show that the two IgA subclasses (IgA1 and IgA2) differ in their effect on immune cells due to distinct binding and signaling properties. Whereas IgA2 acts pro-inflammatory on neutrophils and macrophages, IgA1 does not have pronounced effects. Moreover, IgA1 and IgA2 have different glycosylation profiles, with IgA1 possessing more sialic acid than IgA2. Removal of sialic acid increases the pro-inflammatory capacity of IgA1, making it comparable to IgA2. Of note, disease-specific autoantibodies in patients with rheumatoid arthritis display a shift toward the pro-inflammatory IgA2 subclass, which is associated with higher disease activity. Taken together, these data demonstrate that IgA effector functions depend on subclass and glycosylation, and that disturbances in subclass balance are associated with autoimmune disease.

Purpose: This review examines the broad contexts of the reconstructive and recanalization strategies of the human lacrimal drainage system. Materials and methods: A PubMed search was performed using individually and combination of the terms “lacrimal,” “reconstruction”, “recanalization,” “canaliculus,” “canalicular,” “stenosis,” “obstruction,” “block,” “drainage,” “disorder,” “disease,” “nasolacrimal duct (NLD),” “endoscopy,” “dacryoendoscopy,” “trauma,” “laceration,” “stents,” “repair,” “tubes,” “tear,” “eyelid,” “Sisler,” “trephine,” and “trephination”. Selections from these lists were the basis of examination of reconstruction and recanalization strategies of multiple lacrimal disorders and their outcomes. Results: The major focus areas of this review are obstructions of the canaliculi and the NLD, traumatic involvement of the lacrimal drainage and their reconstruction strategies, and dacryoendoscopy-guided recanalization of the NLDs. The review found evidence for lack of uniformity in accurately defining the concepts of lacrimal drainage stenosis, partial or complete obstructions. Canalicular obstructions are difficult to manage and outcomes depend on the location of the obstruction. High success rates were reported in cases of canalicular lacerations managed by repair and silicone intubation. Controversies exists in the recanalization strategies involving the NLD. In the absence of any current regenerative strategies, NLD recanalization appears to be promising, but skepticism is well justified until its long-term effects are well known. Conclusions: Reconstructive strategies in canalicular trauma are highly successful. Recanalization strategies for the lacrimal drainage system are promising and there is a need to explore stem cells and regenerative modalities to take the lacrimal drainage science a step forward.

Purpose: The meibomian glands are located in the tarsal plate of the upper and lower eyelid and are responsible for the production of a lipid-rich secretion, the meibum, which forms the outer component of the tear film. Meibomian gland dysfunction results in excessive evaporation of the tear film and is the leading cause of dry eye disease (DED). Despite the high prevalence of DED, the etiology of meibomian gland dysfunction is only basically understood. In addition, the molecular mechanisms of meibomian gland maturation and physiological function are currently the focus of research. Methods: A systematic literature search was performed using the main scientific databases, including all relevant published articles up to September 2020. Results: This article provides an overview of the current state of knowledge about meibomian gland stem cells, cell surface marker expression and PPARγ signaling, as well as the pathological causes of meibomian gland dysfunction. Conclusion: Androgen deficiency, hyperkeratinization, PPARγ signaling and inflammatory reactions including neutrophil extracellular traps (NETs) seem to be key factors within the pathological processes of the meibomian gland.

Mechanical aspects play an important role in brain development, function, and disease. Therefore, continuum-mechanics-based computational models are a valuable tool to advance our understanding of mechanics-related physiological and pathological processes in the brain. Currently, mainly phenomenological material models are used to predict the behavior of brain tissue numerically. The model parameters often lack physical interpretation and only provide adequate estimates for brain regions which have a similar microstructure and age as those used for calibration. These issues can be overcome by establishing advanced constitutive models that are microstructurally motivated and account for regional heterogeneities through microstructural parameters.In this work, we perform simultaneous compressive mechanical loadings and microstructural analyses of porcine brain tissue to identify the microstructural mechanisms that underlie the macroscopic nonlinear and time-dependent mechanical response. Based on experimental insights into the link between macroscopic mechanics and cellular rearrangements, we propose a microstructure-informed finite viscoelastic constitutive model for brain tissue. We determine a relaxation time constant from cellular displacement curves and introduce hyperelastic model parameters as linear functions of the cell density, as determined through histological staining of the tested samples. The model is calibrated using a combination of cyclic loadings and stress relaxation experiments in compression. The presented considerations constitute an important step towards microstructure-based viscoelastic constitutive models for brain tissue, which may eventually allow us to capture regional material heterogeneities and predict how microstructural changes during development, aging, and disease affect macroscopic tissue mechanics.