Transcriptome analysis of pterygium and pinguecula reveals evidence of genomic instability associated with chronic inflammation

Solar damage due to ultraviolet radiation (UVR) is implicated in the development of two proliferative lesions of the ocular surface: pterygium and pinguecula. Pterygium and pinguecula specimens were collected, along with adjacent healthy conjunctiva specimens. RNA was extracted and sequenced. Pairwise comparisons were made of differentially expressed genes (DEGs). Computational methods were used for analysis. Transcripts from 18,630 genes were identified. Comparison of two subgroups of pterygium specimens uncovered evidence of genomic instability associated with inflammation and the immune response; these changes were also observed in pinguecula, but to a lesser extent. Among the top DEGs were four genes encoding tumor suppressors that were downregulated in pterygium: C10orf90, RARRES1, DMBT1 and SCGB3A1; C10orf90 and RARRES1 were also downregulated in pinguecula. Ingenuity Pathway Analysis overwhelmingly linked DEGs to cancer for both lesions; however, both lesions are clearly still benign, as evidenced by the expression of other genes indicating their well‐differentiated and non‐invasive character. Pathways for epithelial cell proliferation were identified that distinguish the two lesions, as well as genes encoding specific pathway components. Upregulated DEGs common to both lesions, including KRT9 and TRPV3, provide a further insight into pathophysiology. Our findings suggest that pterygium and pinguecula, while benign lesions, are both on the pathological pathway towards neoplastic trans-formation.Fil: Suarez, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Tufts University School of Medicine; Estados UnidosFil: Echenique, Jose Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Lopez, Juan Manuel. Instituto de Microcirugía Ocular Córdoba; ArgentinaFil: Medina, Esteban Roberto. Instituto de Microcirugia Ocular Cordoba; ArgentinaFil: Irós, Mariano. Instituto de Microcirugia Ocular Cordoba; ArgentinaFil: Serra, Horacio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Fini, M. Elizabeth. Tufts Graduate School Of Biomedical Sciences, Boston; Estados Unido

International Asteroid Warning Network Timing Campaign : 2019 XS

Peer reviewe

Suono e Spettacolo. Athanasius Kircher, un percorso nelle Immagini sonore.

The Society of Jesus made great propaganda efforts throughout the seventeenth century and chose the images and the play as a privileged means to communicate and persuade. Athanasius Kircher, a key figure of the seventeenth century, he decided to dominate the wild nature of sound through Phonurgia Nova, which includes a gallery of powerful symbolic images for Baroque aesthetics. The essay, through the grant of the images from the Library of the Department of Mathematics "Guido Castelnuovo" Sapienza University of Rome, aims to understand, through the pictures offered by Kircher, the sound phenomenon and the spectacle that this produces. In Phonurgia Nova a process of dramatization sound effects takes place, often through machines and "visions" applied to the theatrical reality, as experimental and astonishing environment beloved in baroque. Kircher illustrates the sound through explanatory figures, so to dominate the sound through the eyes. Sound is seen, admired and represented: its spectacle not only takes place through the implementation of sound machines or the "wonders" applied to the theater, but even through images, creating create a sense of wonder in in the erudite person of the seventeenth century

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Therapeutic Potential of the Molecular Chaperone and Matrix Metalloproteinase Inhibitor Clusterin for Dry Eye

Evidence is presented herein supporting the potential of the natural homeostatic glycoprotein CLU (clusterin) as a novel therapeutic for the treatment of dry eye. This idea began with the demonstration that matrix metalloproteinase MMP9 is required for damage to the ocular surface in mouse dry eye. Damage was characterized by degradation of OCLN (occludin), a known substrate of MMP9 and a key component of the paracellular barrier. Following up on this finding, a yeast two-hybrid screen was conducted using MMP9 as the bait to identify other proteins involved. CLU emerged as a strong interacting protein that inhibits the enzymatic activity of MMP9. Previously characterized as a molecular chaperone, CLU is expressed prominently by epithelia at fluid-tissue interfaces and secreted into bodily fluids, where it protects cells and tissues against damaging stress. It was demonstrated that CLU also protects the ocular surface in mouse dry eye when applied topically to replace the natural protein depleted from the dysfunctional tears. CLU is similarly depleted from tears in human dry eye. The most novel and interesting finding was that CLU binds selectively to the damaged ocular surface. In this position, CLU protects against epithelial cell death and barrier proteolysis, and dampens the autoimmune response, while the apical epithelial cell layer is renewed. When present at high enough concentration, CLU also blocks staining by vital dyes used clinically to diagnose dry eye. None of the current therapeutics have this combination of properties to “protect, seal, and heal”. Future work will be directed towards human clinical trials to investigate the therapeutic promise of CLU

Ultrasound Activates the TM ELAM-1/IL-1/NF-B Response: A Potential Mechanism for Intraocular Pressure Reduction after Phacoemulsification

PURPOSE. Elevated intraocular pressure (IOP), the major causal risk factor for glaucoma, often decreases after cataract removal by phacoemulsification ultrasound. In this study, the hypothesis that ultrasound energy propagated through a fluid medium induces a stress response with the potential to lower IOP was investigated. METHODS. Normal and glaucomatous trabecular meshwork (TM) cell culture lines were initiated from tissue isolated from human cadaveric eyes or trabeculectomy specimens. Cultured cells were treated for 60 seconds with a phacoemulsification ultrasound probe set to a power of 70%. Activation of the TM cell-specific stress response was assayed by enzyme-linked immunosorbent assay (ELISA) and immunolocalization. RESULTS. Normal TM cell cultures did not release detectable levels of the stress response protein, IL-1␣, into their culture medium. In contrast, IL-1␣ was easily detected after treatment with ultrasound energy. Consistent with earlier findings, glaucomatous TM cells produced IL-1␣ constitutively, and the level of expression was increased after treatment with phacoemulsification ultrasound. As was previously demonstrated, the stress-regulated transcription factor NF-B was present in the cytoplasm of normal cells, but in the nucleus of glaucomatous cells. After treatment with ultrasound energy, NF-B translocated to the nucleus in the normal cells. Endothelial leukocyteadhesion molecule (ELAM)-1 was not detected in normal TM cells, but was constitutively present on glaucomatous TM cells, consistent with findings in previous work. ELAM-1 expression was induced in normal cells by ultrasound treatment. CONCLUSIONS. A potentially IOP-lowering stress response is induced in TM cells by ultrasound. The findings suggest that this response may be induced clinically during cataract removal by phacoemulsification, and may be one mechanism responsible for the reduction in IOP that often follows this procedure