Untangling the extracellular matrix of idiopathic epiretinal membrane: a path winding among structure, interactomics and translational medicine

Idiopathic epiretinal membranes (iERMs) are fibrocellular sheets of tissue that develop at the vit-reoretinal interface. iERMs consist of cells and extracellular matrix (ECM) formed by a complex array of structural proteins and a large number of proteins that regulate cell-matrix interaction, matrix deposition and remodelling. Many components of the ECM tend to produce a layered pat-tern that can influence the tractional properties of the membranes. We applied a bioinformatics approach on a list of proteins previously identified with an MS-based proteomic analysis on sam-ples of iERM to report the interactome of some key proteins. The performed pathway analysis highlights interactions occurring among ECM molecules, their cell receptors, and intra or extra-cellular proteins that may play a role in matrix biology, in this special context. In particular, integ-rin β1, cathepsin B, epidermal growth factor receptor, protein-glutamine gam-ma-glutamyltransferase 2, and prolow-density lipoprotein receptor-related protein 1 are key hubs in the outlined protein-protein cross-talks. A section on the biomarkers that can be found in the vitreous humor of patients affected by iERM and that can modulate matrix deposition is also pre-sented. Finally, translational medicine in iERM treatment has been summed up taking stock of the techniques that have been proposed for pharmacologic vitreolysi

Dimerization of the C-type lectin-like receptor CD93 promotes its binding to Multimerin-2 in endothelial cells

Blocking the signaling activated by the plasma membrane receptor CD93 has recently been demonstrated a useful tool in antiangiogenic treatment and oncotherapy. In the proliferating endothelium, CD93 regulates cell adhesion, migration, and vascular maturation, yet it is unclear how CD93 interacts with the extracellular matrix activating signaling pathways involved in the vascular remodeling. Here for the first time we show that in endothelial cells CD93 is structured as a dimer and that this oligomeric form is physiologically instrumental for the binding of CD93 to its ligand Multimerin-2. Crystallographic X-ray analysis of recombinant CD93 reveals the crucial role played by the C-type lectin-like and sushi-like domains in arranging as an antiparallel dimer to achieve a functional binding state, providing key information for the future design of new drugs able to hamper CD93 function in neovascular pathologies

Dimerization of the C-type lectin-like receptor CD93 promotes its binding to Multimerin-2 in endothelial cells.

Blocking the signaling activated by the plasma membrane receptor CD93 has recently been demonstrated a useful tool in antiangiogenic treatment and oncotherapy. In the proliferating endothelium, CD93 regulates cell adhesion, migration, and vascular maturation, yet it is unclear how CD93 interacts with the extracellular matrix activating signaling pathways involved in the vascular remodeling. Here for the first time we show that in endothelial cells CD93 is structured as a dimer and that this oligomeric form is physiologically instrumental for the binding of CD93 to its ligand Multimerin-2. Crystallographic X-ray analysis of recombinant CD93 reveals the crucial role played by the C-type lectin-like and sushi-like domains in arranging as an antiparallel dimer to achieve a functional binding state, providing key information for the future design of new drugs able to hamper CD93 function in neovascular pathologies

TGF-β concentrations and activity are down-regulated in the aqueous humor of patients with neovascular age-related macular degeneration

Controversy still exists regarding the role of the TGF-β in neovascular age-related macular degeneration (nAMD), a major cause of severe visual loss in the elderly in developed countries. Here, we measured the concentrations of active TGF-β1, TGF-β2, and TGF-β3 by ELISA in the aqueous humor of 20 patients affected by nAMD, who received 3 consecutive monthly intravitreal injections of anti-VEGF-A antibody. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). The same samples were used in a luciferase-based reporter assay to test the TGF-β pathway activation. Active TGF-β1 concentrations in the aqueous humor were below the minimum detectable dose. Active TGF-β2 concentrations were significantly lower at baseline and at month 1, compared to controls. No significant differences in active TGF-β3 concentration were found among the sample groups. Moreover, TGF-β pathway activation was significantly lower at baseline compared to controls. Our data corroborate an anti-angiogenic role for TGF-β2 in nAMD. This should be considered from the perspective of a therapy using TGF-β inhibitors

Estasi e sgomento. Antologia di poesia barocca ceca

L'antologia contiene una selezione di poesie e brani poetici risalenti a Seicento e Settecento e appartenenti alla letteratura ceca, in traduzione italiana con testo in lingua originale a fronte

Le tempeste dell'ira. Antologia di prosa barcca ceca

Antologia di prosa barocca ceca in traduzione italianaItalian translation of an anthology of Czech baroque texts

Racconti di Malá Strana e altre storie praghesi

Traduzione, condotta con Alena Wildová Tosi, di un'antologia contenente in traduzione italiana alcuni testi della raccolta Racconti di Malá Strana e una selezione di testi narrativi e pubblicistici di Jan Neruda legati alla città di Praga e finora inediti in italiano. La traduzione è corredata di un saggio critico di Annalisa Cosentino, di una prefazione e di un apparato critico a cura di Alena Wildová Tosi.The book contains a selection from the Tales of Malá Strana and several short tales and articles by Jan Neruda in Italian translation. An essay by A. Cosentino and a preface with detailed notes by Alena Wildová Tosi complete the volume

Estasi e sgomento. Antologia di poesia barocca ceca

L'antologia contiene una selezione di poesie e brani poetici risalenti a Seicento e Settecento e appartenenti alla letteratura ceca, in traduzione italiana con testo in lingua originale a fronte

The extracellular matrix complexity of idiopathic epiretinal membranes and the bilaminar arrangement of the associated internal limiting membrane in the posterior retina

Purpose: To study the composition of the internal limiting membrane (ILM) of the retina, the extracellular matrix (ECM) of idiopathic epiretinal membranes (iERM)s and the relationships occurring between the two membranes. Methods: Forty-six iERMs, 24 of them associated with the ILM, were collected and included in this study. The investigation has been carried out by immunofluorescence and confocal microscopy on glutaraldehyde- and osmium-fixed epon-embedded samples and on frozen samples. Sections were double or triple labelled with antibodies against vimentin, collagens I, III, IV, α5(IV) and VI, laminin 1 + 2, laminin α2-, α4-, α5-, β1-, β2-, β3-, γ1- and γ2-chains, entactin and fibronectin. Results: iERMs thickness was not uniform. Almost 14% of iERMs showed thickenings due to folding of their ECM component under the cell layer. The vitreal side of iERMs was often shorter than the attached ILM. In this case, the ILM resulted folded under the iERM. ILMs contained laminin 111, laminin α2-, α5-, β1-, β2-, γ1- chains, entactin, collagens I, α5(IV), [α1(IV)]2α2(IV) and VI. Laminins, entactin and α5(IV) were gathered on the retinal half of the ILM, whereas collagens [α1(IV)]2α2(IV) and I were restricted to the vitreal side. Collagen VI was detected on both sides of the ILM. iERMs expressed laminin 111, collagens III, [α1(IV)]2α2(IV) and VI, entactin and fibronectin. Entactin co-localized with laminins and collagen IV. Conclusions: Analysis of laminins and collagen chains expression indicates that ILM contains laminin 111 (former laminin 1), laminin 521 (former laminin 11), laminin 211 (former laminin 2), collagen [α1(IV)]2α2(IV) and collagen α3(IV)α4(IV)α5. In contrast, iERMs express only collagen [α1(IV)]2α2(IV) and laminin 111. In addition, both iERMs and ILMs contains entactin. The presence of three major constituents of the basement membranes co-localized together in iERMs is suggestive for a deranged process of basement membrane formation which fail to assembly properly. In view of the many interactions occurring among its proteins, the ECM of either the iERMs or the ILMs can account for their reciprocal adhesiveness. In addition, the peculiar deposition of the ECM observed in some samples of iERM is suggestive for its involvement in the formation of macular puckers