Therapeutic approaches with intravitreal injections in geographic atrophy secondary to age-related macular degeneration: current drugs and potential molecules

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory agents. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. Changes in the correct visual acuity and reduction in geographic atrophy progression were evaluated. Several new drugs have shown promising results, including those targeting the complement cascade and neuroprotective agents. The potential action of the two groups of drugs is to block complement cascade upregulation of immunomodulating agents, and to prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. Our analysis indicates that finding treatments for dry AMD will require continued collaboration among researchers to identify additional molecular targets and to fully interrogate the utility of pluripotent stem cells for personalized therapy

Strategies to Use Nanoparticles to Generate CD4 and CD8 Regulatory T Cells for the Treatment of SLE and Other Autoimmune Diseases

Autoimmune diseases are disorders of immune regulation where the mechanisms responsible for self-tolerance break down and pathologic T cells overcome the protective effects of T regulatory cells (Tregs) that normally control them. The result can be the initiation of chronic inflammatory diseases. Systemic lupus erythematosus (SLE) and other autoimmune diseases are generally treated with pharmacologic or biological agents that have broad suppressive effects. These agents can halt disease progression, yet rarely cure while carrying serious adverse side effects. Recently, nanoparticles have been engineered to correct homeostatic regulatory defects and regenerate therapeutic antigen-specific Tregs. Some approaches have used nanoparticles targeted to antigen presenting cells to switch their support from pathogenic T cells to protective Tregs. Others have used nanoparticles targeted directly to T cells for the induction and expansion of CD4+ and CD8+ Tregs. Some of these T cell targeted nanoparticles have been formulated to act as tolerogenic artificial antigen presenting cells. This article discusses the properties of these various nanoparticle formulations and the strategies to use them in the treatment of autoimmune diseases. The restoration and maintenance of Treg predominance over effector cells should promote long-term autoimmune disease remission and ultimately prevent them in susceptible individuals

Management of patients with Graves' disease and orbital involvement: role of spectral domain optical coherence tomography

PURPOSE: To investigate the role of choroidal thickness evaluation with spectral domain optical coherence tomography (SDOCT) and enhanced depth imaging (EDI) technique in the management of patients with Graves' disease and orbitopathy (GO). METHODS: Thirty-six eyes of 18 patients with GO and 36 eyes of 18 age-matched control subjects were included in this retrospective observational study. All the subjects underwent a complete ophthalmological evaluation, including clinical activity score (CAS) and exophthalmometry. The SDOCT images of the choroid were obtained by EDI modality. RESULTS: Choroidal thickness was significantly increased in GO than in control eyes (p < 0.01). A significant correlation was found between choroidal thickness and CAS, proptosis, and the duration of disease (p < 0.05). CONCLUSION: This study shows that choroidal thickness, evaluated with EDI-OCT, is significantly increased in patients with GO and correlates with the activity of the disease, proptosis, and duration of the disease. The choroidal thickening may reflect the ocular hemodynamic changes, and enhanced depth imaging optical coherence tomography may be a useful tool for the evaluation of orbital congestion and management of patients with Graves' disease and orbital involvement

A System for Accessible Artificial Intelligence

While artificial intelligence (AI) has become widespread, many commercial AI systems are not yet accessible to individual researchers nor the general public due to the deep knowledge of the systems required to use them. We believe that AI has matured to the point where it should be an accessible technology for everyone. We present an ongoing project whose ultimate goal is to deliver an open source, user-friendly AI system that is specialized for machine learning analysis of complex data in the biomedical and health care domains. We discuss how genetic programming can aid in this endeavor, and highlight specific examples where genetic programming has automated machine learning analyses in previous projects.Comment: 14 pages, 5 figures, submitted to Genetic Programming Theory and Practice 2017 worksho

Nanoparticles Engineered as Artificial Antigen-Presenting Cells Induce Human CD4+ and CD8+ Tregs That Are Functional in Humanized Mice

Artificial antigen-presenting cells (aAPCs) are synthetic versions of naturally occurring antigen-presenting cells (APCs) that, similar to natural APCs, promote efficient T effector cell responses in vitro. This report describes a method to produce acellular tolerogenic aAPCs made of biodegradable poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and encapsulating IL-2 and TGF-β for a paracrine release to T cells. We document that these aAPCs can induce both human CD4(+) and CD8(+) T cells to become FoxP3(+) T regulatory cells (Tregs). The aAPC NP-expanded human Tregs are functional in vitro and can modulate systemic autoimmunity in vivo in humanized NSG mice. These findings establish a proof-of-concept to use PLGA NPs as aAPCs for the induction of human Tregs in vitro and in vivo, highlighting the immunotherapeutic potential of this targeted approach to repair IL-2 and/or TGF-β defects documented in certain autoimmune diseases such as systemic lupus erythematosus

Leptin as a metabolic link to multiple sclerosis.

Clinical and experimental data, together with epidemiological studies, have suggested that the pathogenesis of multiple sclerosis (MS) might involve factors that link the immune system with metabolic status. Moreover, recent research has shown that leptin, the adipocyte-derived hormone that controls food intake and metabolism, can promote experimental autoimmune encephalomyelitis, an animal model of MS. In patients with MS, the association of leptin with disease activity has been dissected at the molecular level, providing new mechanistic explanations for the role of this hormone in MS. Here, we review the intricate relationship between leptin and other metabolic modulators within a framework that incorporates the latest advances linking the CNS, immune tolerance and metabolic status. We also consider the translational implications of these new findings for improved management of MS