Epigenetics in the Eye: An Overview of the Most Relevant Ocular Diseases.
Ontology highlight
ABSTRACT:
SUBMITTER: Alkozi HA
PROVIDER: S-EPMC5643502 | biostudies-other | 2017
REPOSITORIES: biostudies-other
Publications
Epigenetics in the Eye: An Overview of the Most Relevant Ocular Diseases.
Alkozi Hanan A HA Franco Rafael R Pintor Jesús J JJ
Frontiers in genetics 20171012
Sight for mammals is one of the most appreciated senses. In humans there are several factors that contribute to the increment in all kind of eye diseases. This mini-review will focus on some diseases whose prevalence is steadily increasing year after year for non-genetic reasons, namely cataracts, dry eye, and glaucoma. Aging, diet, inflammation, drugs, oxidative stress, seasonal and circadian style-of-live changes are impacting on disease prevalence by epigenetics factors, defined as stable her ...[more]
Similar Datasets
Project description:BACKGROUND:The optical accessibility of the eye and technological advances in ophthalmic diagnostics have put ophthalmology at the forefront of data-driven medicine. The focus of this study is rare eye disorders, a group of conditions whose clinical heterogeneity and geographic dispersion make data-driven, evidence-based practice particularly challenging. Inter-institutional collaboration and information sharing is crucial but the lack of standardised terminology poses an important barrier. Ontologies are computational tools that include sets of vocabulary terms arranged in hierarchical structures. They can be used to provide robust terminology standards and to enhance data interoperability. Here, we discuss the development of the ophthalmology-related component of two well-established biomedical ontologies, the Human Phenotype Ontology (HPO; includes signs, symptoms and investigation findings) and the Orphanet Rare Disease Ontology (ORDO; includes rare disease nomenclature/nosology). METHODS:A variety of approaches were used including automated matching to existing resources and extensive manual curation. To achieve the latter, a study group including clinicians, patient representatives and ontology developers from 17 countries was formed. A broad range of terms was discussed and validated during a dedicated workshop attended by 60 members of the group. RESULTS:A comprehensive, structured and well-defined set of terms has been agreed on including 1106 terms relating to ocular phenotypes (HPO) and 1202 terms relating to rare eye disease nomenclature (ORDO). These terms and their relevant annotations can be accessed in http://www.human-phenotype-ontology.org/ and http://www.orpha.net/ ; comments, corrections, suggestions and requests for new terms can be made through these websites. This is an ongoing, community-driven endeavour and both HPO and ORDO are regularly updated. CONCLUSIONS:To our knowledge, this is the first effort of such scale to provide terminology standards for the rare eye disease community. We hope that this work will not only improve coding and standardise information exchange in clinical care and research, but also it will catalyse the transition to an evidence-based precision ophthalmology paradigm.
| S-EPMC6327432 | biostudies-literature
Project description:Currently there are no viable treatment options for patients with debilitating inherited retinal degeneration. The vast variability in disease-inducing mutations and resulting phenotypes has hampered the development of therapeutic interventions. Gene therapy is a logical approach, and recent work has focused on ways to optimize vector design and packaging to promote optimized expression and phenotypic rescue after intraocular delivery. In this review, we discuss ongoing ocular clinical trials, which currently use viral gene delivery, but focus primarily on new advancements in optimizing the efficacy of non-viral gene delivery for ocular diseases. Non-viral delivery systems are highly customizable, allowing functionalization to improve cellular and nuclear uptake, bypassing cellular degradative machinery, and improving gene expression in the nucleus. Non-viral vectors often yield transgene expression levels lower than viral counterparts, however their favorable safety/immune profiles and large DNA capacity (critical for the delivery of large ocular disease genes) make their further development a research priority. Recent work on particle coating and vector engineering presents exciting ways to overcome limitations of transient/low gene expression levels, but also highlights the fact that further refinements are needed before use in the clinic.
| S-EPMC4699668 | biostudies-literature
Project description:Network medicine is a molecular-bioinformatic approach analyzing gene-gene interactions that can perturb the human interactome. This review focuses on epigenetic changes involved in several ocular diseases, such as DNA methylation, histone and nonhistone post-translational modifications, and noncoding RNA regulators. Although changes in aberrant DNA methylation play a major role in the pathogenesis of most ocular diseases, histone modifications are seldom investigated. Hypermethylation in TGM-2 and hypomethylation in MMP-2/CD24 promoter genes may play a crucial role in pterygium development; hypermethylation in regulatory regions of GSTP1 and OGG1 genes appear to be diagnostic biomarkers of cataract; hypomethylation of TGF-β1 promoter may trigger glaucoma onset; hypermethylation of the LOXL1 gene might be associated with pseudoexfoliation syndrome. A large panel of upregulated micro-RNAs (miRNAs), including hsa-hsa-miR-494, hsa-let-7e, hsa-miR-513-1, hsa-miR-513-2, hsa-miR-518c, hsa-miR-129-1, hsa-miR-129-2, hsa-miR-198, hsa-miR-492, hsa-miR-498, hsa-miR-320, hsa-miR-503, and hsa-miR-373, ∗ may have a putative role in the development of retinoblastoma. Hypermethylation of H3K4 and hypomethylation of H3K27 at the TGFBIp locus are putative pathogenic mechanisms involved in corneal dystrophies. Determining how, where, and when specific epigenetic changes trigger ocular diseases may provide useful clinical biomarkers for their prevention, diagnosis, and management, as well as innovative drug targets. PF-04523655, a 19-nucleotide methylated double-stranded siRNA targeting the RTP80 gene, showed a dose-related improvement in best-corrected visual acuity (BCVA) in patients affected by diabetic macular edema. The observed results support a clinical network-based research program aimed to clarify the role of epigenetic regulators in the development of ocular diseases and personalized therapy.
| S-EPMC6959156 | biostudies-literature
Project description:Tissue engineering is biomedical engineering that uses suitable biochemical and physicochemical factors to assemble functional constructs that restore or improve damaged tissues. Recently, cell therapies as a subset of tissue engineering have been very promising in the treatment of ocular diseases. One of the most important biophysical factors to make this happen is noninvasive electrical stimulation (ES) to target ocular cells that may preserve vision in multiple retinal and optic nerve diseases. The science of cellular and biophysical interactions is very exciting in regenerative medicine now. Although the exact effect of ES on cells is unknown, multiple mechanisms are considered to underlie the effects of ES, including increased production of neurotrophic agents, improved cell migration, and inhibition of proinflammatory cytokines and cellular apoptosis. In this review, we highlighted the effects of ES on ocular cells, especially on the corneal, retinal, and optic nerve cells. Initially, we summarized the current literature on the in vitro and in vivo effects of ES on ocular cells and then we provided the clinical studies describing the effect of ES on ocular complications. For each area, we used some of the most impactful articles to show the important concepts and results that advanced the state of these interactions. We conclude with reflections on emerging new areas and perspectives for future development in this field.
| S-EPMC8612806 | biostudies-literature
Project description:The aim of the present study was to evaluate sleep and mood disorders in patients with irritating ocular diseases. The study design was a cross-sectional/case-control study conducted in six eye clinics. Out of 715 outpatients diagnosed with irritating ocular surface diseases and initially enrolled, 301 patients with dry eye disease (DED) and 202 age-matched control participants with other ocular surface diseases were analyzed. The mean Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) scores were 6.4 ± 3.2 and 11.1 ± 5.7 for severe DED (n = 146), 5.5 ± 3.3 and 9.8 ± 4.0 for mild DED (n = 155), 5.5 ± 3.1 and 9.5 ± 6.6 for chronic conjunctivitis (n = 124), and 5.0 ± 3.3 and 8.9 ± 5.3 for allergic conjunctivitis (n = 78). There were significant differences among these diagnostic groups for PSQI (P < 0.05). Regression analysis of patients with DED revealed the PSQI and HADS scores were significantly correlated with the severity of DED (P < 0.05). Our results demonstrate that sleep quality in patients with DED is significantly worse than in patients with other irritating ocular surface diseases and it is correlated with the severity of DED.
| S-EPMC4772386 | biostudies-other
Project description:Hearing loss (HL) is one of the most common sensory impairments worldwide and represents a critical medical and public health issue. Since the mid-1900s, great efforts have been aimed at understanding the etiology of both syndromic and non-syndromic HL and identifying correlations with specific audiological phenotypes. The extraordinary discoveries in the field of molecular genetics during the last three decades have contributed substantially to the current knowledge. Next-generation sequencing technologies have dramatically increased the diagnostic rate for genetic HL, enabling the detection of novel variants in known deafness-related genes and the discovery of new genes implicated in hearing disease. Overall, genetic factors account for at least 40% of the cases with HL, but a portion of affected patients still lack a definite molecular diagnosis. Important steps forward have been made, but many aspects still have to be clarified. In particular, the role of epigenetics in the development, function and pathology of hearing is a research field that still needs to be explored. This research is extremely challenging due to the time- and tissue-dependent variability of the epigenetic changes. Multisystem diseases are expected to be investigated at first: specific epi-signatures have been identified for several syndromic disorders and represent potential markers for molecular diagnostics.
| S-EPMC8628574 | biostudies-literature
Project description:Forkhead transcription factors comprise a large family of proteins with diverse functions during development. Recently, there has been accumulating evidence that several members of this family of proteins play an important role in the development of the vertebrate retina. Here, we summarize the cumulative data which demonstrates the integral role that forkhead factors play in cell cycle control of retinal precursors, as well as in cell fate determination, during retinal development. The expression patterns for 14 retinal expressed forkhead transcription factors are presented with an emphasis on comparing the expression profiles across species. The functional data regarding forkhead gene products expressed within the retina are discussed. As presented, these data suggest that forkhead gene products contribute to the complex regulation of proliferation and differentiation of retinal precursors during vertebrate eye development.
| S-EPMC6326383 | biostudies-literature
Project description:Objective This paper reviews ocular pain with the main focus on ocular surface discomfort and dry eye pain. Anatomy, physiology, epidemiology, assessment, and treatment are discussed in this paper. Methods A PubMed search was conducted for studies published from 2000 to 2019 on the anatomy, pathophysiology, epidemiology, assessment, and treatment of ocular pain. Reviews, meta-analyses, and randomized clinical trials were included. Inclusion criteria focused on ocular surface discomfort, dry eye pain and neuropathic pain. Results A total of 112 articles were found through searches, 45 of which were selected and studied in this review. Discussion Pain in general can be acute or chronic. Acute pain is usually a physiologic response to a serious damage to the tissues and alleviates with pain relief treatments. Chronic pain is defined as the persistence of pain for more than three months. From another point of view, pain has been classified into either nociceptive or neuropathic. Nociceptive pain is a physiologic response to a noxious stimulus. Both central and peripheral nervous systems can be involved in the development of a neuropathic pain, which is characterized by positive or negative sensory signs, a pain perceived disproportionate to a noxious stimulus, and/or not responsive to analgesics. Chronic pain usually has a neuropathic component. Ocular surface pain is a well-known complaint after any corneal surgery. This is mainly due to abnormal regeneration of damaged corneal nerve endings and abnormal connections with adjacent nerve endings which produce spontaneous activity. Tear hyperosmolarity and the resultant ocular surface inflammation can also trigger voluntary activity of corneal nerve endings. Referral pain to the first and second division of the trigeminal nerve has been reported. Interference with vision and even sleep, which is out of proportion to the examination are among patients’ complaints. All of these elements proposed the new concept of ocular neuropathic pain syndrome. The first step in conventional evaluation of ocular discomfort is search for tear insufficiency. Pathologies of lid and blinking as well as conjunctival irregularities should be addressed. Anti-inflammatory agents and, in resistant cases, systemic neuromodulators are shown to be helpful. Education on behavioral changes and reassurance are essential steps. Considering the neuropathic origin for the ocular pain, treatment modalities used for such pain in other parts of the body can be considered for this syndrome.
| S-EPMC7524198 | biostudies-literature
Project description:Increasing evidence suggests that epigenetic modifications, including changes in DNA methylation, covalent modifications of histone tails, and gene silencing mediated by non-coding RNA molecules, play a substantial role in the pathogenesis of autoimmune disorders and might be seen as the result of environmental insults that trigger these conditions. Studies in cells and tissues of patients with autoimmune thyroid diseases (AITD), and particularly in Graves' disease (GD) and Hashimoto's thyroiditis (HT), are increasingly revealing altered epigenetic marks and resultant deregulation of gene expression levels, but the available data are still limited to be translated into the clinical settings. Particularly, genome-wide methylation and histone tail modification screenings are limited to a few studies in GD patients, and the diagnostic values of the observed epigenetic changes or their potential prognostic utility are still unclear. Similarly, data concerning microRNA expression in AITD patients are largely descriptive and not yet translated into the clinics. In addition, studies relating certain environmental exposures to specific epigenetic changes in AITD and studies evaluating the crosstalk between different epigenetic mechanisms are largely missing. In summary, despite that there is a clear evidence of epigenetic impairment in AITD, further research is required for a better understanding of the epigenetic networks involved in disease pathogenesis, thereby opening the way for potential diagnostic and prognostic tools, as well as for epigenetic interventions in the patients.
| S-EPMC5489553 | biostudies-literature
Project description:BACKGROUND:The use of blood-derived eye drops for topical treatment of ocular surface diseases has progressively increased in recent years. MATERIALS AND METHODS:To evaluate the use of serum eye drops in ocular surface disorders, we performed a systematic search of the literature. RESULTS:In this systematic review, we included 19 randomised controlled trials (RCTs) investigating the use of serum eye drops in 729 patients compared to controls. For the quantitative synthesis, we included only 10 RCTs conducted in patients with dry eye syndrome comparing autologous serum to artificial tears. At 2-6 weeks, no clear between-group differences in Schirmer test (MD 1.05; 95% CI: -0.17-2.26) and in fluorescein staining (MD -0.61; 95% CI: -1.50-0.28) were found (very low-quality evidence, down-graded for inconsistency, serious risk of biases, and serious imprecision). Slightly higher increase in tear film break-up time (TBUT) scores in autologous serum compared to control (MD 2.68; 95% CI: 1.33-4.03), and greater decrease in ocular surface disease index (OSDI) in autologous serum compared to control (MD -11.17; 95% CI: -16.58 - -5.77) were found (low quality evidence, down-graded for serious risk of bias, and for inconsistency). For the Schirmer test, fluorescein staining and TBUT, data were also available at additional follow-up timing (2-12 months): no clear between-group differences were found, and the quality of the evidence was graded as low/very-low. CONCLUSIONS:In patients with dry eye syndrome, it is unclear whether or not the use of autologous serum compared to artificial tears increases Schirmer test and fluorescein staining scores at short-term and medium-/long-term follow up. Some benefit at short-term follow up for the outcome of TBUT and OSDI was observed, but the quality of the evidence was low.
| S-EPMC6596382 | biostudies-literature