Müller glial cells located in the peripheral retina are more susceptible to high pressure: implications for glaucoma.

Background: Glaucoma, a progressive neurodegenerative disease, is a leading cause of irreversible vision loss worldwide. This study aims to elucidate the critical role of Müller glia (MG) in the context of retinal ganglion cell (RGC) death, particularly focusing on the influence of peripheral MG sensitivity to high pressure (HP).

Methods: Co-cultures of porcine RGCs with MG were isolated from both the central and peripheral regions of pig retinas and subjected to both normal and HP conditions.

Neuroinflammation and gliosis in the injured and contralateral retinas after unilateral optic nerve crush.

The main purpose of this study is to analyze the effects of unilateral optic nerve crush in the gene expression of pro- and anti-inflammatory mediators, and gliosis markers in injured and contralateral retinas. Retinas from intact, unilaterally optic nerve injured or sham-operated C57BL/6J mice were analyzed 1, 3, 9 and 30 days after the surgery (n = 5/group and time point) and the relative expression of TGF-β1, IL-1β, TNF-α, Iba1, AQP4, GFAP, MHCII, and TSPO was analyzed in injured and contralateral using qPCR. The results indicated that compared with intact retinas, sham-operated animals showed an early (day 1) upregulation of IL-1β, TNF-α and TSPO and a late (day 30) upregulation of TNF-α.

Intraocular implants loaded with AR agonist rescue retinal ganglion cells from ischemic damage.

Retinal ganglion cell (RGC) loss underlies several conditions which give rise to significant visual compromise, including glaucoma and ischaemic optic neuropathies. Neuroprotection of RGCs is a clinical well-defined unmet need in these diseases, and adenosine A receptor (AR) activation emerges as a therapeutic pharmacological approach to protect RGCs. A porous biodegradable intraocular implant loaded with 2-Cl-IB-MECA (selective AR agonist) was used as a strategy to protect RGCs.

Building an IoT Platform Based on Service Containerisation.

IoT platforms have become quite complex from a technical viewpoint, becoming the cornerstone for information sharing, storing, and indexing given the unprecedented scale of smart services being available by massive deployments of a large set of data-enabled devices. These platforms rely on structured formats that exploit standard technologies to deal with the gathered data, thus creating the need for carefully designed customised systems that can handle thousands of heterogeneous data sensors/actuators, multiple processing frameworks, and storage solutions. We present the SCoT2.

Microglial Extracellular Vesicles as Vehicles for Neurodegeneration Spreading.

Microglial cells are the neuroimmune competent cells of the central nervous system. In the adult, microglia are responsible for screening the neuronal parenchyma searching for alterations in homeostasis. Chronic neuroinflammation plays a role in neurodegenerative disease.

Activation of Adenosine A Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure.

Glaucoma is a progressive chronic retinal degenerative disease and a leading cause of global irreversible blindness, characterized by optic nerve damage and retinal ganglion cell (RGC) death. Elevated intraocular pressure (IOP) is a main risk factor of glaucoma. Neuroinflammation plays an important role in glaucoma.

Exosomes derived from microglia exposed to elevated pressure amplify the neuroinflammatory response in retinal cells.

Glaucoma is a degenerative disease that causes irreversible loss of vision and is characterized by retinal ganglion cell (RGC) loss. Others and we have demonstrated that chronic neuroinflammation mediated by reactive microglial cells plays a role in glaucomatous pathology. Exosomes are extracellular vesicles released by most cells, including microglia, that mediate intercellular communication.

Activation of adenosine A receptor protects retinal ganglion cells from degeneration induced by ocular hypertension.

Glaucoma is a progressive chronic retinal degenerative disease and a leading cause of global irreversible blindness. This disease is characterized by optic nerve damage and retinal ganglion cell (RGC) death. The current treatments available target the lowering of intraocular pressure (IOP), the main risk factor for disease onset and development.

Microglia Contribution to the Regulation of the Retinal and Choroidal Vasculature in Age-Related Macular Degeneration.

The retina is a highly metabolically active tissue with high-level consumption of nutrients and oxygen. This high metabolic demand requires a properly developed and maintained vascular system. The retina is nourished by two systems: the central retinal artery that supplies the inner retina and the choriocapillaris that supplies the outer retina and retinal pigment epithelium (RPE).

Neuroprotective Strategies for Retinal Ganglion Cell Degeneration: Current Status and Challenges Ahead.

The retinal ganglion cells (RGCs) are the output cells of the retina into the brain. In mammals, these cells are not able to regenerate their axons after optic nerve injury, leaving the patients with optic neuropathies with permanent visual loss. An effective RGCs-directed therapy could provide a beneficial effect to prevent the progression of the disease.

Keep an eye on adenosine: Its role in retinal inflammation.

Adenosine is an endogenous purine nucleoside ubiquitously distributed throughout the body that interacts with G protein-coupled receptors, classified in four subtypes: AR, AR, AR and AR. Among the plethora of functions of adenosine, it has been increasingly recognized as a key mediator of the immune response. Neuroinflammation is a feature of chronic neurodegenerative diseases and contributes to the pathophysiology of several retinal degenerative diseases.

Intravitreal injection of adenosine A receptor antagonist reduces neuroinflammation, vascular leakage and cell death in the retina of diabetic mice.

Diabetic retinopathy is a major complication of diabetes mellitus and a leading cause of blindness. The pathogenesis of diabetic retinopathy is accompanied by chronic low-grade inflammation. Evidence shows that the blockade of adenosine A receptors (AR) affords protection to the retina through the control of microglia-mediated neuroinflammation.

Porous poly(ε-caprolactone) implants: A novel strategy for efficient intraocular drug delivery.

This work reports the development of porous poly (ε-caprolactone) (PCL)-based intraocular implants, prepared by green supercritical carbon dioxide (scCO) foaming/mixing method (SFM), to produce implants that degrade faster than typical slow-degrading PCL-based implants. The higher porosities and surface areas of these implants led to faster degradation rates at in vitro accelerated alkaline conditions than low porosity/surface area implants prepared by hot melting processing. These porous implants also presented distinct (faster) release rates of a test-drug (dexamethasone).

Blockade of microglial adenosine A receptor suppresses elevated pressure-induced inflammation, oxidative stress, and cell death in retinal cells.

Glaucoma is a retinal degenerative disease characterized by the loss of retinal ganglion cells and damage of the optic nerve. Recently, we demonstrated that antagonists of adenosine A receptor (A R) control retinal inflammation and afford protection to rat retinal cells in glaucoma models. However, the precise contribution of microglia to retinal injury was not addressed, as well as the effect of A R blockade directly in microglia.

In Vivo Characterization of Corneal Changes in a Type 1 Diabetic Animal Model.

Diabetes mellitus (DM) is a metabolic disease that affects 9% of the adult population, promoting an increase in glucose concentration that affects the corneal structure, namely, its thickness, as well as the constituents and flow of the aqueous humor. In this study, high-frequency transducers (20-MHz and 50-MHz) were used to measure and characterize changes in the corneal and aqueous humor in streptozotocin-induced type 1 diabetic rats followed over 8 weeks. Increases of 24.

Sweet Stress: Coping With Vascular Dysfunction in Diabetic Retinopathy.

Oxidative stress plays key roles in the pathogenesis of retinal diseases, such as diabetic retinopathy. Reactive oxygen species (ROS) are increased in the retina in diabetes and the antioxidant defense system is also compromised. Increased ROS stimulate the release of pro-inflammatory cytokines, promoting a chronic low-grade inflammation involving various signaling pathways.

Subtle thinning of retinal layers without overt vascular and inflammatory alterations in a rat model of prediabetes.

Purpose: Diabetic retinopathy is a neurovascular disease characterized by increased permeability of the blood-retinal barrier, changes in the neural components of the retina, and low-grade chronic inflammation. Diabetic retinopathy is a major complication of diabetes; however, the impact of a prediabetic state on the retina remains to be elucidated. The aim of this study was to assess possible early retinal changes in prediabetic rats, by evaluating changes in the integrity of the blood-retinal barrier, the retinal structure, neural markers, and inflammatory mediators.

Impact of type 1 diabetes mellitus and sitagliptin treatment on the neuropeptide Y system of rat retina.

Background: Neuropeptide Y (NPY) is a neuromodulator that is expressed in the retina. Increasing evidence suggests that NPY has pronounced anti-inflammatory effects, which might depend on the inhibition of dipeptidyl-peptidase-IV (DPP-IV). The aim of this study was to investigate the impact of type 1 diabetes mellitus (DM) and sitagliptin, a DPP-IV inhibitor, on the NPY system in the retina using an animal model.

Elevated Pressure Changes the Purinergic System of Microglial Cells.

Glaucoma is the second cause of blindness worldwide and is characterized by the degeneration of retinal ganglion cells (RGCs) and optic nerve atrophy. Increased microglia reactivity is an early event in glaucoma that may precede the loss of RGCs, suggesting that microglia and neuroinflammation are involved in the pathophysiology of this disease. Although global changes of the purinergic system have been reported in experimental and human glaucoma, it is not known if this is due to alterations of the purinergic system of microglial cells, the resident immune cells of the central nervous system.

Treatment with A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage.

Transient retinal ischemia is a major complication of retinal degenerative diseases and contributes to visual impairment and blindness. Evidences indicate that microglia-mediated neuroinflammation has a key role in the neurodegenerative process, prompting the hypothesis that the control of microglia reactivity may afford neuroprotection to the retina against the damage induced by ischemia-reperfusion (I-R). The available therapeutic strategies for retinal degenerative diseases have limited potential, but the blockade of adenosine A receptor (AR) emerges as candidate strategy.

Calcium Dobesilate Is Protective against Inflammation and Oxidative/Nitrosative Stress in the Retina of a Type 1 Diabetic Rat Model.

Calcium dobesilate (CaD) has been prescribed to some patients in the early stages of diabetic retinopathy to delay its progression. We previously reported that the treatment of diabetic animals (4 weeks of diabetes) with CaD, during the last 10 days of diabetes, prevents blood-retinal barrier breakdown. Here, we aimed to investigate whether later treatment of diabetic rats with CaD would reverse inflammatory processes in the retina.

Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype.

Vitamin C is essential for the development and function of the central nervous system (CNS). The plasma membrane sodium-vitamin C cotransporter 2 (SVCT2) is the primary mediator of vitamin C uptake in neurons. SVCT2 specifically transports ascorbate, the reduced form of vitamin C, which acts as a reducing agent.