1,721,188 research outputs found
Inherited Retinal Dystrophies: The role of gene expression regulators
No full textInherited Retinal Dystrophies (IRDs) are a clinically and genetically heterogeneous group of rare disorders characterized by a significant impairment in retinal function and vision. More than 150 genes have been associated with retinal dystrophies and the genetic overlap among different IRDs renders diagnosis and prognosis challenging. In this In Focus article, we give a summary on the pathogenic role of gene expression regulators in IRDs. Emphasis is given on key transcription factors that participate to regulatory gene networks controlling photoreceptor specification and maintenance, and their possible relevance as therapeutic targets. The increasing knowledge on the composition and function of these transcriptional regulatory networks indicates that intervening on transcription factors may be instrumental for a more effective treatment of some forms of IRDs, although the development of appropriate molecular tools to target them remains a formidable challenge
Non-coding RNAs in retinal development and function
No full textAccumulating evidence on the role of non-protein-coding RNA sequences in the regulation of gene expression is greatly expanding our understanding of the flow of genetic information within biological systems. The interplay between protein-coding and non-coding RNAs (ncRNAs) is essential for tissue development, homeostasis, and function. NcRNAs can be divided in short ncRNAs, whose main subtype is represented by microRNAs, and long ncRNAs, which constitute a more heterogeneous class. The retina is a light-sensitive tissue consisting of highly interconnected cell types and is the primary target of many genetic diseases. Among these, the genetically heterogeneous group of inherited retinal diseases (IRDs) represents the most frequent monogenic cause of visual impairment that can ultimately lead to blindness. Here, we provide an overview on the role of ncRNAs in retinal development and function with an emphasis on microRNAs and on different types of long ncRNAs. We also review how sequence variations in ncRNAs can play a pathogenic role in IRDs as well as in multifactorial ocular disorders. These data indicate that a comprehensive study of the contribution of ncRNAs to the mutation repertoire associated with retinal disease can shed light on previously unknown pathophysiological mechanisms and open new therapeutic avenues. We conclude that a more comprehensive dissection of the pathogenic role of non-coding RNAs in retinal function and disease will not only improve our diagnostic ability, but will allow the development of novel targeted therapies for ocular disease
The role of miRNAs in retinal physiology and in Inherited Retinal Disorders
No full text: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Several studies have highlighted their role as key regulators of different physiological processes that underly retinal homeostasis. Recent evidence suggests that they play a role not only at the intracellular level but also extracellularly, participating in cell-cell crosstalk by being transported via extracellular vesicles (EVs). Moreover, changes in miRNA expression levels have been associated with different forms of retinal diseases, such as Inherited Retinal Diseases (IRDs). IRDs are a group of genetic disorders characterized by photoreceptor cell death and retinal degeneration. Notably, miRNAs can simultaneously regulate multiple molecular pathways associated with disease initiation and progression. Finally, modulation of miRNAs through upregulation or downregulation has shown beneficial effects in different IRD mouse models. Here, we provide a comprehensive overview of retinal miRNA expression profiles in both healthy and IRD conditions and explore their potential as therapeutic targets for clinical applications
Sophisticated Gene Regulation for a Complex Physiological System: The Role of Non-coding RNAs in Photoreceptor Cells
No full textPhotoreceptors (PRs) are specialized neuroepithelial cells of the retina responsible for sensory transduction of light stimuli. In the highly structured vertebrate retina, PRs have a highly polarized modular structure to accommodate the demanding processes of phototransduction and the visual cycle. Because of their function, PRs are exposed to continuous cellular stress. PRs are therefore under pressure to maintain their function in defiance of constant environmental perturbation, besides being part of a highly sophisticated developmental process. All this translates into the need for tightly regulated and responsive molecular mechanisms that can reinforce transcriptional programs. It is commonly accepted that regulatory non-coding RNAs (ncRNAs), and in particular microRNAs (miRNAs), are not only involved but indeed central in conferring robustness and accuracy to developmental and physiological processes. Here we integrate recent findings on the role of regulatory ncRNAs (e.g., miRNAs, lncRNAs, circular RNAs, and antisense RNAs), and of their contribution to PR pathophysiology. We also outline the therapeutic implications of translational studies that harness ncRNAs to prevent PR degeneration and promote their survival and function
- …
