1,720,968 research outputs found
Identificazione di nuovi meccanismi coinvolti nella disfunzione dell’Epitelio Pigmentato Retinico come bersagli terapeutici per la Degenerazione Maculare Legata all’Età.
No full textThis project take place in a research field that aims to deepen the knowledge of human retinal degenerations. In this wide field, the present study focuses on the study of AMD, which is considered a multifactorial disorder caused by both environmental and genetic risk factors. AMD incidence increases with age, and it is going to raise dramatically due to life expectancy increase in the modern age. In fact, according to the World Health Organization (WHO), over two billion people worldwide suffer from vision-related problems. AMD could be classified into two main forms with different features: dry AMD and wet (or exudative) AMD. The available therapies to date are not resolutive; thus, the research on this topic is continuously evolving to find new targets for the development of effective treatments. During AMD, retinal antioxidant machinery is impaired, leading to oxidative stress burden, which is therefore considered one of the main risk factors for this pathology. In this project, we focused our attention on the degenerative events occurring in the Retinal Pigment Epithelium (RPE) during AMD and the analysis of possible protective molecules. RPE plays a key role in the maintenance of retinal homeostasis through its several functions; however, during AMD, oxidative stress triggers several RPE alterations which culminate in a failure of RPE performance and its consequent degeneration. On these bases, here we investigated the potential protective outcomes of Curcumin and L-DOPA on RPE cells challenged with oxidative stress. Both these molecules have already shown protective effects against retinal degenerations; thus, we aimed at identifying new mechanisms of action of these molecules. We analysed two main aspects linked to RPE dysfunction during AMD: cellular homeostasis and melanogenesis. In particular, we provided new understanding on the dose-dependent role of Curcumin; We found that low concentrations maintain RPE cells homeostasis while high concentrations caused a harmful stimulus to the cells, inducing proliferation arrest and autophagy activation. These data support the application of Curcumin for ocular pathologies characterized by different features. Furthermore, we identified a new mechanism of action of curcumin, demonstrating that the low concentrations prevented oxidative stress-induced cell death by inhibiting the activity of SIRT1, an enzyme involved in AMD progression. In the second part of the project, we evaluated the role of L-DOPA on cellular homeostasis and melanogenesis. L-DOPA was able to prevent oxidative stress-induced cell death, acting on different pathways including mitochondrial homeostasis and autophagy. We demonstrated that the protective effect of L-DOPA is related to the activation of its specific receptor on RPE cells, GPR143, as also demonstrated by Intracellular Calcium increase. Furthermore, the activation of GPR143 by L-DOPA induced a downstream event related to the the modulation of Vascular Endothelial Growth Factor (VEGF) and Pigmented Epithelium-derived factor (PEDF), the main growth factors involved in RPE function. L-DOPA administration was also associated with the up-regulation of Tyrosinase, demonstrating the role of L-DOPA in enhancing melanogenesis process. In the last part of this project, through an in silico study, we also provided evidence of the interaction of L-DOPA with another receptor involved in melanogenesis, Melanocortin 1 receptor (MC1R). All together, these results provided new understanding of RPE degenerative events caused by oxidative stress and underlined new mechanisms of action of Curcumin and L-DOPA, two promising molecules for the treatment of AMD
Towards the identification of L-DOPA mechanisms of action on retinal pigment epithelial cells: insights for Age Related Macular Degeneration
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An overview of retinal light damage models for preclinical studies on age-related macular degeneration: identifying molecular hallmarks and therapeutic targets
Full text linkAge-related macular degeneration (AMD) is a complex, multifactorial disease leading to progressive and irreversible retinal degeneration, whose pathogenesis has not been fully elucidated yet. Due to the complexity and to the multiple features of the disease, many efforts have been made to develop animal models which faithfully reproduce the overall AMD hallmarks or that are able to mimic the different AMD stages. In this context, light damage (LD) rodent models of AMD represent a suitable and reliable approach to mimic the different AMD forms (dry, wet and geographic atrophy) while maintaining the time-dependent progression of the disease. In this review, we comprehensively reported how the LD paradigms reproduce the main features of human AMD. We discuss the capability of these models to broaden the knowledge in AMD research, with a focus on the mechanisms and the molecular hallmarks underlying the pathogenesis of the disease. We also critically revise the remaining challenges and future directions for the use of LD models
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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