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Discovery of insulin. If the symptoms of diabetes have been known since Antiquity, it is at the end of the 19th century that several investigators searched for the active substance of the pancreas and endeavoured to produce extracts that lowered blood and urine glucose and decreased polyuria in pancreatectomized dogs. The breakthrough came 100 years ago when the team of Frederick Banting, Charles Best and James Collip, working in the Department of Physiology, headed by John MacLeod at the University of Toronto, managed to obtain pancreatic extracts that could be used to treat patients and rescue them from the edge of death by starvation, the only treatment then available.

Insulin: A 100-Year-Old Discovery With a Fascinating History.

Diabetes has been known since antiquity. We present here a historical perspective on the concepts and ideas regarding the physiopathology of the disease, on the progressive focus on the pancreas, in particular on the islets discovered by Langerhans in 1869, leading to the iconic experiment of Minkowski and von Mering in 1889 showing that pancreatectomy in a dog induced polyuria and diabetes mellitus. Subsequently, multiple investigators searched for the active substance of the pancreas and some managed to produce extracts that lowered blood glucose and decreased polyuria in pancreatectomized dogs but were too toxic to be administered to patients.

Topical treatment with a mu opioid receptor agonist alleviates corneal allodynia and corneal nerve sensitization in mice.

Corneal pain is considered to be a core symptom of ocular surface disruption and inflammation. The management of this debilitating condition is still a therapeutic challenge. Recent evidence supports a role of the opioid system in the management of corneal nociception.

Chronic dry eye induced corneal hypersensitivity, neuroinflammatory responses, and synaptic plasticity in the mouse trigeminal brainstem.

Background: Dry eye disease (DED) is a multifactorial disease associated with ocular surface inflammation, pain, and nerve abnormalities. We studied the peripheral and central neuroinflammatory responses that occur during persistent DED using molecular, cellular, behavioral, and electrophysiological approaches.

Methods: A mouse model of DED was obtained by unilateral excision of the extraorbital lachrymal gland (ELG) and Harderian gland (HG) of adult female C57BL/6 mice.

Correction to: Tyrosine-hydroxylase immunoreactivity in the mouse transparent brain and adrenal glands.

Unfortunately, the given name and family name of the fourth author was incorrectly tagged in the xml data, therefore it is abbreviated wrongly as ''Goazigo AR'' in Pubmed. The correct given name is Annabelle and family name is Reaux‑Le Goazigo.

[Understanding chronic ocular pain].

Dry eye disease (DED) is a common chronic condition with multifactorial etiologies that is increasing in prevalence worldwide, up to 20% in the elderly. The economic burden and impact of DED on vision, quality of life, work productivity, psychological and physical impact of pain, are considerable. Chronic ocular pain is the most common symptom of DED and there is currently no topical ocular analgesic therapy available to treat this debilitating disease.

Tyrosine-hydroxylase immunoreactivity in the mouse transparent brain and adrenal glands.

Working on catecholamine systems for years, the neuropharmacologist Arvid Carlsson has made a number of important and pioneering discoveries, which have highlighted the key role of these neuronal and peripheral neurotransmitters in brain functions and adrenal regulations. Since then, major advances have been made concerning the distribution of the catecholaminergic systems in particular by studying their rate-limiting enzyme, tyrosine hydroxylase (TH). Recently new methods of tissue transparency coupled with in toto immununostaining and three-dimensional (3D) imaging technologies allow to precisely map TH immunoreactive pathways in the mouse brain and adrenal glands.

Central CCL2 signaling onto MCH neurons mediates metabolic and behavioral adaptation to inflammation.

Sickness behavior defines the endocrine, autonomic, behavioral, and metabolic responses associated with infection. While inflammatory responses were suggested to be instrumental in the loss of appetite and body weight, the molecular underpinning remains unknown. Here, we show that systemic or central lipopolysaccharide (LPS) injection results in specific hypothalamic changes characterized by a precocious increase in the chemokine ligand 2 (CCL2) followed by an increase in pro-inflammatory cytokines and a decrease in the orexigenic neuropeptide melanin-concentrating hormone (MCH).

Prostaglandin EP2 receptor signaling protects human trabecular meshwork cells from apoptosis induced by ER stress through down-regulation of p53.

E-prostanoid receptor subtype 2 (EP2) agonists are currently under clinical development as hypotensive agents for the treatment of ocular hypertension. However, the effects of EP2 receptor agonists on trabecular meshwork (TM) alterations leading to primary open-angle glaucoma (POAG) are still unknown. Here, we evaluated whether EP2 receptor activation exhibits protective functions on TM cell death induced by endoplasmic reticulum (ER) stress.

Activation of Prostaglandin FP and EP2 Receptors Differently Modulates Myofibroblast Transition in a Model of Adult Primary Human Trabecular Meshwork Cells.

Purpose: Prostaglandin F2α analogues are the first-line medication for the treatment of ocular hypertension (OHT), and prostanoid EP2 receptor agonists are under clinical development for this indication. The goal of this study was to investigate the effects of F prostanoid (FP) and EP2 receptor activation on the myofibroblast transition of primary trabecular meshwork (TM) cells, which could be a causal mechanism of TM dysfunction in glaucoma.

Methods: Human primary TM cells were treated with either latanoprost or butaprost and TGF-β2.

Bilateral neuroinflammatory processes in visual pathways induced by unilateral ocular hypertension in the rat.

Background: Glaucoma is one of the leading causes of irreversible blindness in the world. The major risk factor is elevated intraocular pressure (IOP) leading to progressive retinal ganglion cell (RGC) death from the optic nerve (ON) to visual pathways in the brain. Glaucoma has been reported to share mechanisms with neurodegenerative disorders.

Ocular inflammation induces trigeminal pain, peripheral and central neuroinflammatory mechanisms.

Ocular surface diseases are among the most frequent ocular pathologies, with prevalence ranging from 20% of the general population. In addition, ocular pain following corneal injury is frequently observed in clinic. The aim of the study was to characterize the peripheral and central neuroinflammatory process in the trigeminal pathways in response to cornea alteration induced by chronic topical instillations of 0.

Intraocular pressure reduction and neuroprotection conferred by bone marrow-derived mesenchymal stem cells in an animal model of glaucoma.

Introduction: Glaucoma is a sight-threatening retinal neuropathy associated with elevated intraocular pressure (IOP) due to degeneration and fibrosis of the trabecular meshwork (TM). Glaucoma medications aim to reduce IOP without targeting the specific TM pathology, Bone-marrow mesenchymal stem cells (MSCs) are used today in various clinical studies. Here, we investigated the potential of MSCs therapy in an glaucoma-like ocular hypertension (OHT) model and decipher in vitro the effects of MSCs on primary human trabecular meshwork cells.

Combined 3DISCO clearing method, retrograde tracer and ultramicroscopy to map corneal neurons in a whole adult mouse trigeminal ganglion.

Tissue clearing and subsequent imaging of intact transparent tissues have provided an innovative way to analyze anatomical pathways in the nervous system. In this study, we combined a recent 3-dimensional imaging of solvent cleared organ (3DISCO) procedure, light-sheet microscopy, fluorescent retrograde tracer, and Imaris software to 3D map corneal sensory neurons within a whole adult mouse trigeminal ganglion (TG). We first established the optimized steps to easily and rapidly clear a fixed TG.

Opioid and chemokine receptor crosstalk: a promising target for pain therapy?

Chemokines and opioids are important regulators of immune, inflammatory and neuronal responses in peripheral and central pain pathways. Recent studies have provided insights into the functional interactions between chemokine receptors and opioid receptors, and their role in pain modulation. In this Progress article, we discuss how crosstalk between these two systems might provide a molecular and cellular framework for the development of novel analgesic therapies for the management of acute and/or chronic pain.

[Chemokines and attraction of myeloid cells in peripheral neuropathic pains].

Chronic neuropathic pain has become a real social issue, due to the difficulty of its treatment and by the major impairment to quality of life that it causes in every day behavior. Understanding neurobiological basis and pathophysiological causes of diverse painful syndromes constantly evolves and reports the complexity of its mechanisms. Unfortunately this complexity makes it difficult to discover effective treatments against chronic pain syndromes, in particular as regards peripheral neuropathic pains.

[Glaucoma today: detection and therapeutic progress].

Second leading cause of blindness worldwide, glaucoma is an optic neuropathy related mainly but not exclusively to an increase of intraocular pressure. Angle closure glaucoma is related to a blockade of aqueous humor to the trabecular meshwork, whereas open-angle glaucoma is a degeneration of the trabecular meshwork, the filter that allows aqueous outflow from the eye. Many improvements have been made in terms of diagnosis, follow-up and treatments, although the treatment of glaucoma is restricted to control intraocular pressure, in order to prevent optic nerve degeneration or to stop the progression of the disease toward blindness.

[Chemokines: new insights in the treatment of glaucoma and inflammatory diseases of the ocular surface].

The celebrations of the 200th anniversary of Claude Bernard's birth (1813) give us the opportunity to recall all the pioneer work carried out by the great physiologist, which still remains relevant in both scientific and medical fields. The description that tissues are "floating in a liquid milieu" bringing survival molecules and allowing homeostasis, is particularly illustrated in the physiopathology of glaucoma. Second leading cause of blindness worldwide, glaucoma is an optic neuropathy mainly related to an increase of intraocular pressure.

Effects of benzalkonium chloride on THP-1 differentiated macrophages in vitro.

Purpose: To characterize the effects of benzalkonium chloride (BAK) in THP-1 differentiated cells in vitro.

Methods: Macrophages were obtained after differentiation of THP-1 cells, a human monocytic leukemia cell line. Macrophages were exposed for 24 h to 33 nM (10(-5)%) benzalkonium chloride (BAK), 10 nM dinitrochlorobenzene (DNCB), 100 ng/mL lipopolysaccharide (LPS), 5 ng/mL tumor necrosis factor alpha (TNF-α) or phosphate buffered saline (PBS) as controls.