scholarly journals Innovative Strategies for Treating Retinal Diseases

2019 ◽  
Vol 75 (6) ◽  
pp. 287-295
Author(s):  
Zbyněk Straňák ◽  
Bohdan Kousal ◽  
Taras Ardan ◽  
Miroslav Veith
Keyword(s):  
Gene Therapy ◽  
Retinal Pigment ◽  
Retinal Diseases ◽  
Retinal Prostheses ◽  
Innovative Strategies ◽  
Current State ◽  
The Future ◽  
Rpe Transplantation ◽  
Basic Characteristics ◽  
Interesting Development

Objective: The aim of this comprehensive paper is to acquaint the readers with innovative approaches in the treatment of retinal diseases, which could in the coming years to get into clinical practice. Retinal prostheses, retinal pigment epithelial (RPE) transplantation, gene therapy and optogenetics will be described in this paper. Methodology: Describing the basic characteristics and mechanisms of different types of therapy and subsequently literary minireview clarifying the current state of knowledge in the area. Results: Retinal prostheses, RPE transplantation, gene therapy and optogenetics offer yet unexplored possibilities and are considered as the future of treatment of retinal diseases where classical pharmacotherapy or surgical treatment are no longer sufficient. However, all these methods challenge not only in the innovative technical implementation itself, but also for the ethical, administrative and economic demands. Conclusion: There will be certainly interesting development in the treatment of retinal diseases, but it is not possible to fully estimate which modality of treatment will be dominant in the future.

scholarly journals Gene Therapy in Inherited Retinal Diseases: An Update on Current State of the Art

2021 ◽  
Vol 8 ◽  
Author(s):  
Alessia Amato ◽  
Alessandro Arrigo ◽  
Emanuela Aragona ◽  
Maria Pia Manitto ◽  
Andrea Saladino ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Practice ◽  
State Of The Art ◽  
Therapeutic Option ◽  
Retinal Disease ◽  
Retinal Diseases ◽  
Current State ◽  
The Future ◽  
Genetic Features ◽  
Clinical Background

Background: Gene therapy cannot be yet considered a far perspective, but a tangible therapeutic option in the field of retinal diseases. Although still confined in experimental settings, the preliminary results are promising and provide an overall scenario suggesting that we are not so far from the application of gene therapy in clinical settings. The main aim of this review is to provide a complete and updated overview of the current state of the art and of the future perspectives of gene therapy applied on retinal diseases.Methods: We carefully revised the entire literature to report all the relevant findings related to the experimental procedures and the future scenarios of gene therapy applied in retinal diseases. A clinical background and a detailed description of the genetic features of each retinal disease included are also reported.Results: The current literature strongly support the hope of gene therapy options developed for retinal diseases. Although being considered in advanced stages of investigation for some retinal diseases, such as choroideremia (CHM), retinitis pigmentosa (RP), and Leber's congenital amaurosis (LCA), gene therapy is still quite far from a tangible application in clinical practice for other retinal diseases.Conclusions: Gene therapy is an extremely promising therapeutic tool for retinal diseases. The experimental data reported in this review offer a strong hope that gene therapy will be effectively available in clinical practice in the next years.

scholarly journals Adeno-Associated Viral Vectors as a Tool for Large Gene Delivery to the Retina

Genes ◽  
2019 ◽  
Vol 10 (4) ◽  
pp. 287 ◽  
Author(s):  
Trapani
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Diseases ◽  
Considerable Effort ◽  
Safety And Efficacy ◽  
Large Gene ◽  
Packaging Capacity ◽  
Large Genes

Gene therapy using adeno-associated viral (AAV) vectors currently represents the most promising approach for the treatment of many inherited retinal diseases (IRDs), given AAV’s ability to efficiently deliver therapeutic genes to both photoreceptors and retinal pigment epithelium, and their excellent safety and efficacy profiles in humans. However, one of the main obstacles to widespread AAV application is their limited packaging capacity, which precludes their use from the treatment of IRDs which are caused by mutations in genes whose coding sequence exceeds 5 kb. Therefore, in recent years, considerable effort has been made to identify strategies to increase the transfer capacity of AAV vectors. This review will discuss these new developed strategies, highlighting the advancements as well as the limitations that the field has still to overcome to finally expand the applicability of AAV vectors to IRDs due to mutations in large genes.

scholarly journals Gene Therapy to the Retina and the Cochlea

2021 ◽  
Vol 15 ◽  
Author(s):  
Ryan Crane ◽  
Shannon M. Conley ◽  
Muayyad R. Al-Ubaidi ◽  
Muna I. Naash
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Gene Delivery ◽  
Genome Editing ◽  
Retinal Diseases ◽  
Preclinical Development ◽  
Hearing Disorders ◽  
Gene Therapies ◽  
Current State ◽  
Sensory Disorders

Vision and hearing disorders comprise the most common sensory disorders found in people. Many forms of vision and hearing loss are inherited and current treatments only provide patients with temporary or partial relief. As a result, developing genetic therapies for any of the several hundred known causative genes underlying inherited retinal and cochlear disorders has been of great interest. Recent exciting advances in gene therapy have shown promise for the clinical treatment of inherited retinal diseases, and while clinical gene therapies for cochlear disease are not yet available, research in the last several years has resulted in significant advancement in preclinical development for gene delivery to the cochlea. Furthermore, the development of somatic targeted genome editing using CRISPR/Cas9 has brought new possibilities for the treatment of dominant or gain-of-function disease. Here we discuss the current state of gene therapy for inherited diseases of the retina and cochlea with an eye toward areas that still need additional development.

Molecular imaging of gene therapy. The future in Parkinson's disease therapy?

2005 ◽  
Vol 32 (S 4) ◽  
Author(s):  
A.H Jacobs ◽  
R Hilker ◽  
L Burghaus ◽  
W.D Heiss
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Molecular Imaging ◽  
Disease Therapy ◽  
The Future

Remedies for Breach of Contract: The Future Development of Scots Law in its European and International Context

1997 ◽  
Vol 1 (2) ◽  
pp. 200-226 ◽  
Author(s):  
Hector L MacQueen
Keyword(s):  
Future Development ◽  
European Contract ◽  
Breach Of Contract ◽  
International Context ◽  
The United Kingdom ◽  
Current State ◽  
The Future ◽  
University Of Edinburgh ◽  
International Conventions ◽  
Law Commission

This paper,first presented on 21 October 1995 at ajoint seminar ofthe Scottish Law Commission and the Faculty of Law, University of Edinburgh, on the subject of breach of contract, considers the future development of the law in this area, first by considering its history and current state in comparative terms and drawing the conclusion that it is characterised by a mixture of Civilian and Common Law elements; second, by comparing Scots law with the provisions on breach contained in recently published proposals for a harmonised law of contract (the UNIDROIT Principles of International Commercial Contracts, the Principles of European Contract Law prepared by the Lando Commission, and the draft “code”for the United Kingdom prepared on behalf of the English Law Commission by Harvey McGregor in the late 1960s) and in international conventions on the sale of goods. Although Scots law emerges reasonably wellfrom this exercise, there are a number of points to be taken on board in any future reform, as well as some insights into important underlying principles.

SiRNA technology, the gene therapy of the future?

2008 ◽  
Vol 149 (4) ◽  
pp. 153-159 ◽  
Author(s):  
Zsuzsanna Rácz ◽  
Péter Hamar
Keyword(s):  
Gene Therapy ◽  
Short Interfering Rna ◽  
The Future ◽  
Interfering Rna

A genetikában új korszak kezdődött 17 éve, amikor a petúniában felfedezték a koszuppressziót. Később a koszuppressziót azonosították a növényekben és alacsonyabb rendű eukariótákban megfigyelt RNS-interferenciával (RNSi). Bár a növényekben ez ősi vírusellenes gazdaszervezeti védekezőmechanizmus, emlősökben az RNSi élettani szerepe még nincs teljesen tisztázva. Az RNSi-t rövid kettős szálú interferáló RNS-ek (short interfering RNA, siRNS) irányítják. A jelen cikkben összefoglaljuk az RNSi történetét és mechanizmusát, az siRNS-ek szerkezete és hatékonysága közötti összefüggéseket, a célsejtbe való bejuttatás virális és nem virális módjait. Az siRNS-ek klinikai alkalmazásának legfontosabb akadálya az in vivo alkalmazás. Bár a hidrodinamikus kezelés állatokban hatékony, embereknél nem alkalmazható. Lehetőséget jelent viszont a szervspecifikus katéterezés. A szintetizált siRNS-ek ismert mellékhatásait szintén tárgyaljuk. Bár a génterápia ezen új területén számos problémával kell szembenézni, a sikeres in vitro és in vivo kísérletek reményt jelentenek emberi betegségek siRNS-sel történő kezelésére.

Artistic Challenges within Control Societies: Big Data and Democratic Resistance

MedienJournal ◽  
2017 ◽  
Vol 38 (4) ◽  
pp. 50-61 ◽  
Author(s):  
Jan Jagodzinski
Keyword(s):  
Big Data ◽  
Gilles Deleuze ◽  
Data Archive ◽  
Current State ◽  
The Future ◽  
The Way

This paper will first briefly map out the shift from disciplinary to control societies (what I call designer capitalism, the idea of control comes from Gilles Deleuze) in relation to surveillance and mediation of life through screen cultures. The paper then shifts to the issues of digitalization in relation to big data that have the danger of continuing to close off life as zoë, that is life that is creative rather than captured via attention technologies through marketing techniques and surveillance. The last part of this paper then develops the way artists are able to resist the big data archive by turning the data in on itself to offer viewers and participants a glimpse of the current state of manipulating desire and maintaining copy right in order to keep the future closed rather than being potentially open.

Cartographic production in Russia: main stages and trends

2020 ◽  
Vol 963 (9) ◽  
pp. 30-43
Author(s):  
M.Yu. Orlov
Keyword(s):  
Chronological Order ◽  
Xviii Century ◽  
New Methods ◽  
Current State ◽  
Factors Influencing ◽  
The Future ◽  
History Of ◽  
State Enterprises ◽  
Further Development

Studying the current state of cartography and ways of further developing the industry, the role of the map in the future of the society, new methods of promoting cartographic products is impossible without a deep scientific analyzing all the paths, events and factors influencing its formation and development throughout all the historic steps of cartographic production in Russia. In the article, the history of cartographic production in Russia is considered together with the development of private, state and military cartography, since, despite some differences, they have a common technical, technological and production basis. The author describes the stages of originating, formation and growth of industrial cartographic production from the beginning of the XVIII century until now. The connection between the change of political formations and technological structures with the mentioned stages of maps and atlases production is considered. Each stage is studied in detail, a step-by-step analysis was carried out, and the characteristics of each stage are described. All the events and facts are given in chronological order, highlighting especially significant moments influencing the evolution of cartographic production. The data on the volumes of printing and sales of atlases and maps by commercial and state enterprises are presented. The main trends and lines of further development of cartographic production in Russia are studied.

scholarly journals Relative Contribution of Different Mitochondrial Oxidative Phosphorylation Components to the Retinal Pigment Epithelium Barrier Function: Implications for RPE-Related Retinal Diseases

2021 ◽  
Vol 22 (15) ◽  
pp. 8130
Author(s):  
Michael H. Guerra ◽  
Thangal Yumnamcha ◽  
Lalit P. Singh ◽  
Ahmed S. Ibrahim
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Barrier Function ◽  
Complex I ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Diseases ◽  
Dependent Manner ◽  
Pigment Epithelial ◽  
Dose Dependent

Disruption of retinal pigment epithelial (RPE) barrier integrity is involved in the pathology of several blinding retinal diseases including age-related macular degeneration (AMD) and diabetic retinopathy (DR), but the underlying causes and pathophysiology are not completely well-defined. Mitochondria dysfunction has often been considered as a potential candidate implicated in such a process. In this study, we aimed to dissect the role of different mitochondrial components; specifically, those of oxidative phosphorylation (OxPhos), in maintaining the barrier functionality of RPE. Electric cell-substrate impedance sensing (ECIS) technology was used to collect multi-frequency electrical impedance data to assess in real-time the barrier formation of the RPE cells. For this purpose, the human retinal pigment epithelial cell line—ARPE-19—was used and treated with varying concentrations of specific mitochondrial inhibitors that target different steps in OxPhos: Rotenone for complex I (the largest protein complex in the electron transport chain (ETC)); oligomycin for ATP synthase; and carbonyl cyanide-p-trifluoromethoxyphenyl hydrazone (FCCP) for uncoupling ATP synthesis from the accompanying ETC. Furthermore, data were modeled using the ECIS-Zθ software to investigate in depth the effects of these inhibitors on three separate barrier parameters: cell–cell interactions (Rb), cell–matrix interactions (α), and the cell membrane capacitance (Cm). The viability of ARPE-19 cells was determined by lactate dehydrogenase (LDH) Cytotoxicity Assay. The ECIS program’s modeling demonstrated that FCCP and thus OxPhos uncoupling disrupt the barrier function in the ARPE-19 cells across all three components of the total resistance (Rb, α, and Cm) in a dose-dependent manner. On the other hand, oligomycin and thus ATP synthase inhibition mostly affects the ARPE-19 cells' attachment to their substrate evident by a significant decrease in α resistance in a dose-dependent manner, both at the end and throughout the duration of the experiment. On the contrary, rotenone and complex I inhibition mostly affect the ARPE-19 paracellular resistance Rb in a dose-dependent manner compared to basolateral resistance α or Cm. Our results clearly demonstrate differential roles for different mitochondrial components in maintaining RPE cell functionality in which uncoupling of OxPhos is a major contributing factor to the disruption barrier function. Such differences can be used in investigating gene expression as well as for screening of selective agents that improve the OxPhos coupling efficiency to be used in the therapeutic approach for treating RPE-related retinal diseases.

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