Neuroinflammation and galectins: a key relationship in neurodegenerative diseases.

Neurodegeneration is a pathological condition that is associated with the loss of neuronal function and structure. In neurodegenerative diseases, mounting evidence indicates that neuroinflammation is a common factor that contributes to neuronal damage and neurodegeneration. Neuroinflammation is characterized by the activation of microglia, the neuroimmune cells of the central nervous system (CNS), which have been implicated as active contributors to neuronal damage. Glycan structure modification is defining the outcome of neuroinflammation and neuronal regeneration; moreover, the expression of galectins, a group of lectins that specifically recognize ß-galactosides, has been proposed as a key factor in neuronal regeneration and modulation of the inflammatory response. Of the different galectins identified, galectin-1 stimulates the secretion of neurotrophic factors in astrocytes and promotes neuronal regeneration, whereas galectin-3 induces the proliferation of microglial cells and modulates cell apoptosis. Galectin-8 emerged as a neuroprotective factor, which, in addition to its immunosuppressive function, could generate a neuroprotective environment in the brain. This review describes the role of galectins in the activation and modulation of astrocytes and microglia and their anti- and proinflammatory functions within the context of neuroinflammation. Furthermore, it discusses the potential use of galectins as a therapeutic target for the inflammatory response and remodeling in damaged tissues in the central nervous system.

The therapeutic potential of galectin-1 and galectin-3 in the treatment of neurodegenerative diseases.

Introduction: Neuroinflammation has been proposed as a common factor and one of the main inducers of neuronal degeneration. Galectins are a group of ß-galactoside-binding lectins, that play an important role in the immune response, adhesion, proliferation, differentiation, migration and cell growth. Up to 15 members of the galectin's family have been identified; however, the expression of galectin-1 and galectin-3 has been considered a key factor in neuronal regeneration and modulation of the inflammatory response. Galectin-1 is necessary to stimulate the secretion of neurotrophic factors in astrocytes and promoting neuronal regeneration. In contrast, galectin-3 fosters the proliferation of microglial cells and modulates cellular apoptosis, therefore these proteins are considered a useful alternative for the treatment of degenerative diseases.Areas covered: This review describes the roles of galectin-1 and galectin-3 in the modulation of neuroinflammation and their potential as therapeutic targets in the treatment for neurodegenerative diseases.Expert opinion: Although data in the literature vary, the effects of galectin-1 and galectin-3 on the activation and modulation of astrocytes and microglia has been described. Due to its anti-inflammatory effects, galectin-1 is proposed as a molecule with therapeutic potential, whereas the inhibition of galectin-3 could contribute to reduce the neuroinflammatory response in neurodegenerative diseases.

Whole exome profiling and mutational analysis of Ocular Surface Squamous Neoplasia.

PURPOSE: To determine genetic mutational profiles in patients with Ocular Surface Squamous Neoplasia (OSSN) using whole exome sequencing. METHODS: Prospective, case-series study. Patient recruitment was conducted in a single tertiary referral center from April to September 2017. Specimens were obtained by incisional biopsies of tumors from ten eyes with histopathologic confirmation of OSSN. DNA whole exome sequencing and mutation analysis were performed. RESULTS: Ten patients with clinically-diagnosed OSSN underwent DNA whole exome sequencing analysis. Deleterious mutations in 305 genes known to drive tumor development and progression were found. These mutations centered around two main pathways: DNA repair/cell cycle and development/growth. All ten samples had at least one mutation in a DNA repair/cell cycle gene and all but one sample had one in a development/growth gene. The most common mutation was found in TP53 and HGF (both present in 50% of cases) and mutually exclusive mutations were found in BRCA1 and BRCA2 (50% of cases). Mutations in APC, MSH6, PDGFRA, and PTCH1 were found in 40% of cases. Global mutation analysis identified ultraviolet induced radiation as the only mutational signature present in the dataset. CONCLUSIONS: Mutations found in samples from patients with OSSN are mainly induced by ultraviolet radiation and occur within two main pathways related to DNA repair/cell cycle and development/growth. There are many clinically available drugs and several others being evaluated in clinical trials that target the genes found mutated in this study, offering new therapeutic options for OSSN.

Current Anti-Integrin Therapy for Ocular Disease.

The integrin family of cell adhesion molecules mediates homeostasis, signal transduction, and various other interactions between the cell and the extracellular matrix. Integrins are type-1 transmembrane glycoproteins located on the cell surface, widely expressed in leukocytes, which play an important role in the inflammatory pathway. The purpose of this review is to summarize the current state of anti-integrin therapy and to assess ongoing clinical trials in ocular disease. We performed a search on PubMed, CINAHL, and Embase for the published literature available using the MeSH terms: "integrin therapy" and "αLß2," "α4ß1" and "α4ß7," "αvß3," "αvß5," and "αvß1" and/or "ophthalmology," and "clinical trials." We used no language restrictions. We generated searches to account for synonyms of these keywords and MESH headings as follows: (1) "integrin," "therapy," or "treatment"; (2) "clinical trials," "ophthalmology," or "ocular." In addition, the analysis included phase 2 and phase 3 clinical trials with a minimal follow-up of six months. Integrin antagonists have shown their capacity to improve signs and symptoms of patients with dry eye disease, age-related macular degeneration, diabetic macular edema, and vitreomacular traction.

Effect of phacoemulsification on intraocular pressure in patients with primary open angle glaucoma and pseudoexfoliation glaucoma.

AIM: To compare the effect of phacoemulsification on intraocular pressure (IOP) in patients with primary open angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG). METHODS: A retrospective comparative case series conducted at the Glaucoma Department at the Association to Prevent Blindness in Mexico. The study enrolled consecutive patients having phacoemulsification with intraocular lens (IOL) implantation and a diagnosis of POAG or PXG. Data about IOP values and number of glaucoma medications used was collected at baseline, 1, 3, 6 and 12mo postoperatively. RESULTS: The study enrolled 88 patients (88 eyes). After phacoemulsification, there was a statistically significant reduction in IOP values and glaucoma medications use compared to baseline in both POAG and PXG patients (P<0.001). In the POAG group, a 20% decrease in IOP values was evidenced, and a 56.5% reduction in the number of medications used at the one-year follow-up. The PXG group showed a 20.39%, and a 34.46% decrease in IOP and number of medications used, respectively. A significant difference in the mean ΔIOP (postoperative changes in IOP) was evidenced between groups (P=0.005). The reduction of the postsurgical IOP mean values in both groups, the POAG group showed a greater reduction in IOP values compared to the PXG group. CONCLUSION: In both types of glaucoma, phacoemulsification cataract surgery can result in a significant IOP reduction (20%) over a 12mo follow-up period. The number of medications used is also significantly reduced up to 12mo after surgery, especially in the PXG group.