scholarly journals Zebrafish Model in Ophthalmology to Study Disease Mechanism and Drug Discovery

2021 ◽  
Vol 14 (8) ◽  
pp. 716
Author(s):  
Yiwen Hong ◽  
Yan Luo
Keyword(s):  
Drug Discovery ◽  
Behavioral Assessment ◽  
Age Related Macular Degeneration ◽  
Disease Mechanism ◽  
Zebrafish Model ◽  
Age Related ◽  
Eye Disorders ◽  
Vertebrate Model ◽  
Drug Treatments ◽  
Novel Drug

Visual impairment and blindness are common and seriously affect people’s work and quality of life in the world. Therefore, the effective therapies for eye diseases are of high priority. Zebrafish (Danio rerio) is an alternative vertebrate model as a useful tool for the mechanism elucidation and drug discovery of various eye disorders, such as cataracts, glaucoma, diabetic retinopathy, age-related macular degeneration, photoreceptor degeneration, etc. The genetic and embryonic accessibility of zebrafish in combination with a behavioral assessment of visual function has made it a very popular model in ophthalmology. Zebrafish has also been widely used in ocular drug discovery, such as the screening of new anti-angiogenic compounds or neuroprotective drugs, and the oculotoxicity test. In this review, we summarized the applications of zebrafish as the models of eye disorders to study disease mechanism and investigate novel drug treatments.

Common age-related eye diseases and visual impairment

2017 ◽  
pp. 1165-1170
Author(s):  
Jacqueline Chua ◽  
Ching-Yu Cheng ◽  
Tien Yin Wong
Keyword(s):  
Diabetic Retinopathy ◽  
Visual Impairment ◽  
Macular Degeneration ◽  
Refractive Error ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Eye Disorders ◽  
Appropriate Treatment ◽  
Uncorrected Refractive Error

General physicians have an essential role in preventing vision loss in older people. However, most vision-threatening eye disorders are initially asymptomatic and often go underdiagnosed. Therefore screening, early detection, and timely intervention are important in their management. The most common cause of visual impairment is uncorrected or undercorrected refractive error, followed by cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy. Spectacles and cataract surgery can successfully restore sight for uncorrected refractive error and cataract, respectively. Visual impairment as a result of age-related macular degeneration, glaucoma, and diabetic retinopathy can be prevented with appropriate treatment if they are identified early enough. This chapter provides an overview of common age-related eye disease and visual impairment.

scholarly journals EyeDiseases: an integrated resource for dedicating to genetic variants, gene expression and epigenetic factors of human eye diseases

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Jian Yuan ◽  
Fukun Chen ◽  
Dandan Fan ◽  
Qi Jiang ◽  
Zhengbo Xue ◽  
...  
Keyword(s):  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Omics Data ◽  
Diverse Range ◽  
Human Eye ◽  
Age Related ◽  
Eye Disorders ◽  
Disease Associated Genes ◽  
Highly Correlated ◽  
Candidate Loci

Abstract Eye diseases are remarkably common and encompass a large and diverse range of morbidities that affect different components of the visual system and visual function. With advances in omics technology of eye disorders, genome-scale datasets have been rapidly accumulated in genetics and epigenetics field. However, the efficient collection and comprehensive analysis of different kinds of omics data are lacking. Herein, we developed EyeDiseases (https://eyediseases.bio-data.cn/), the first database for multi-omics data integration and interpretation of human eyes diseases. It contains 1344 disease-associated genes with genetic variation, 1774 transcription files of bulk cell expression and single-cell RNA-seq, 105 epigenomics data across 185 kinds of human eye diseases. Using EyeDiseases, we investigated SARS-CoV-2 potential tropism in eye infection and found that the SARS-CoV-2 entry factors, ACE2 and TMPRSS2 are highly correlated with cornea and keratoconus, suggest that ocular surface cells are susceptible to infection by SARS-CoV-2. Additionally, integrating analysis of Age-related macular degeneration (AMD) GWAS loci and co-expression data revealed 9 associated genes involved in HIF-1 signaling pathway and voltage-gate potassium channel complex. The EyeDiseases provides a valuable resource for accelerating the discovery and validation of candidate loci and genes contributed to the molecular diagnosis and therapeutic vulnerabilities with various eyes diseases.

scholarly journals Integrated Approaches to Drug Discovery for Oxidative Stress-Related Retinal Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Yuhei Nishimura ◽  
Hideaki Hara
Keyword(s):  
Oxidative Stress ◽  
Drug Discovery ◽  
Biological Networks ◽  
Target Selection ◽  
Age Related Macular Degeneration ◽  
Functional Networks ◽  
Retinal Diseases ◽  
Drug Discovery Process ◽  
Age Related ◽  
Selection For

Excessive oxidative stress induces dysregulation of functional networks in the retina, resulting in retinal diseases such as glaucoma, age-related macular degeneration, and diabetic retinopathy. Although various therapies have been developed to reduce oxidative stress in retinal diseases, most have failed to show efficacy in clinical trials. This may be due to oversimplification of target selection for such a complex network as oxidative stress. Recent advances in high-throughput technologies have facilitated the collection of multilevel omics data, which has driven growth in public databases and in the development of bioinformatics tools. Integration of the knowledge gained from omics databases can be used to generate disease-related biological networks and to identify potential therapeutic targets within the networks. Here, we provide an overview of integrative approaches in the drug discovery process and provide simple examples of how the approaches can be exploited to identify oxidative stress-related targets for retinal diseases.

scholarly journals An orthotopic glioblastoma animal model suitable for high-throughput screenings

2018 ◽  
Vol 20 (11) ◽  
pp. 1475-1484 ◽  
Author(s):  
Linda Pudelko ◽  
Steven Edwards ◽  
Mirela Balan ◽  
Daniel Nyqvist ◽  
Jonathan Al-Saadi ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
Large Scale ◽  
Light Sheet ◽  
Time Lapse ◽  
Zebrafish Model ◽  
Light Sheet Microscopy ◽  
Disease Biology ◽  
Vertebrate Model

Abstract Background Glioblastoma (GBM) is an aggressive form of brain cancer with poor prognosis. Although murine animal models have given valuable insights into the GBM disease biology, they cannot be used in high-throughput screens to identify and profile novel therapies. The only vertebrate model suitable for large-scale screens, the zebrafish, has proven to faithfully recapitulate biology and pathology of human malignancies, and clinically relevant orthotopic zebrafish models have been developed. However, currently available GBM orthotopic zebrafish models do not support high-throughput drug discovery screens. Methods We transplanted both GBM cell lines as well as patient-derived material into zebrafish blastulas. We followed the behavior of the transplants with time-lapse microscopy and real-time in vivo light-sheet microscopy. Results We found that GBM material transplanted into zebrafish blastomeres robustly migrated into the developing nervous system, establishing an orthotopic intracranial tumor already 24 hours after transplantation. Detailed analysis revealed that our model faithfully recapitulates the human disease. Conclusion We have developed a robust, fast, and automatable transplantation assay to establish orthotopic GBM tumors in zebrafish. In contrast to currently available orthotopic zebrafish models, our approach does not require technically challenging intracranial transplantation of single embryos. Our improved zebrafish model enables transplantation of thousands of embryos per hour, thus providing an orthotopic vertebrate GBM model for direct application in drug discovery screens.

scholarly journals MicroRNA and vascular pathology of the eye

2020 ◽  
pp. 5-9
Author(s):  
LK Moshetova ◽  
SA Usharova ◽  
KI Turkina ◽  
DA Sychev ◽  
IN Saburina
Keyword(s):  
Retinal Vein Occlusion ◽  
Scientific Community ◽  
Age Related Macular Degeneration ◽  
Vascular Pathology ◽  
Diagnostic Biomarkers ◽  
Vein Occlusion ◽  
Age Related ◽  
Eye Disorders ◽  
Quality Of Medical Care

Since the discovery of microRNAs just a few decades ago, our knowledge of these molecules and their potential as diagnostic biomarkers and therapeutic targets has significantly expanded. There is an ongoing discussion in the scientific community about the possibility of using microRNA for the diagnosis of cardiovascular diseases. It has been shown recently that levels of some microRNAs vary in vascular eye disorders, such as age-related macular degeneration and diabetic retinopathy. However, despite serious advances in our understanding of microRNA’s role in eye pathology, we still do not know whether it is possible to use microRNA as a biomarker for central retinal vein occlusion. Perhaps, the discovery of such candidate microRNAs will help in making the timely diagnosis and improve the quality of medical care in patients with retinal vein occlusion.

scholarly journals A longitudinal study to assess the frequency and cost of antivascular endothelial therapy, and inequalities in access, in England between 2005 and 2015

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e018289 ◽  
Author(s):  
William Hollingworth ◽  
Tim Jones ◽  
Barnaby C Reeves ◽  
Tunde Peto
Keyword(s):  
Longitudinal Study ◽  
Diabetic Macular Oedema ◽  
Cost Effective ◽  
Age Related Macular Degeneration ◽  
Geographical Variations ◽  
Anti Vegf ◽  
Age Related ◽  
Eye Disorders ◽  
Effective Care ◽  
Endothelial Growth Factor

ObjectivesHigh-cost antivascular endothelial growth factor (anti-VEGF) medicines for eye disorders challenge ophthalmologists and policymakers to provide fair access for patients while minimising costs. We describe the growth in the use and costs of these medicines and measure inequalities in access.DesignLongitudinal study using Hospital Episode Statistics (2005/2006 to 2014/2015) and hospital prescribing cost reports (2008/2009 to 2015/2016). We used Poisson regression to estimate standardised rates and explore temporal and geographical variations.SettingNational Health Service (NHS) care in England.PopulationPatients receiving anti-VEGF injections for age-related macular degeneration, diabetic macular oedema and other eye disorders.InterventionsHigher-cost drugs (ranibizumab or aflibercept) recommended by the National Institute for Health and Care Excellence or lower-cost drug (bevacizumab) not licensed for eye disorders.Main outcome measuresNational procedure rates and variation between and within clinical commissioning groups (CCGs). Cost of ranibizumab and aflibercept prescribing.ResultsInjection procedures increased by 215% between 2010/2011 and 2014/2015. In 2014/2015 there were 388 031 procedures (714 per 100 000). There is no evidence that the dramatic growth in rates is slowing down. Since 2010/2011 the estimated cost of ranibizumab and aflibercept increased by 247% to £447 million in 2015/2016, equivalent to the entire annual budget of a CCG. There are large inequalities in access; in 2014/2015 procedure rates in a ‘high use’ CCG were 9.08 times higher than in a ‘low use’ CCG. In the South-West of England there was twofold variation in injections per patient per year (range 2.9 to 5.9).ConclusionsThe high and rising cost of anti-VEGF therapy affects the ability of the NHS to provide care for other patients. Current regulations encourage the increasing use of ranibizumab and aflibercept rather than bevacizumab, which evidence suggests is more cost-effective. NHS patients in England do not have equal access to the most cost-effective care.

Common age-related eye diseases and visual impairment

2017 ◽  
pp. 1165-1170
Author(s):  
Jacqueline Chua ◽  
Ching-Yu Cheng ◽  
Tien Yin Wong
Keyword(s):  
Diabetic Retinopathy ◽  
Visual Impairment ◽  
Macular Degeneration ◽  
Refractive Error ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Eye Disorders ◽  
Appropriate Treatment ◽  
Uncorrected Refractive Error

General physicians have an essential role in preventing vision loss in older people. However, most vision-threatening eye disorders are initially asymptomatic and often go underdiagnosed. Therefore, screening, early detection, and timely intervention are important in their management. The most common cause of visual impairment is uncorrected or under-corrected refractive error, followed by cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy. Spectacles and cataract surgery can successfully restore sight for uncorrected refractive error and cataract, respectively. Visual impairment as a result of age-related macular degeneration, glaucoma, and diabetic retinopathy can be prevented with appropriate treatment if they are identified early enough. This chapter provides an overview of common age-related eye disease and visual impairment.

scholarly journals Reporting of Safety Events during Anti-VEGF Treatment: Pharmacovigilance in a Noninterventional Trial

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Focke Ziemssen ◽  
Thomas Hammer ◽  
Matthias Grueb ◽  
Bettina Mueller ◽  
Hüsnü Berk ◽  
...  
Keyword(s):  
Real World ◽  
Age Related Macular Degeneration ◽  
System Organ Class ◽  
Intravitreal Ranibizumab ◽  
Outcome Severity ◽  
Age Related ◽  
Eye Disorders ◽  
Ocean Study ◽  
Medical Dictionary ◽  
Number Of Injections

Aim. The prospective, noninterventional OCEAN study assessed the safety of intravitreal ranibizumab injections for treatment of neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion under real-world conditions in Germany. Methods. Adults receiving ≥1 ranibizumab (0.5 mg) injections were recruited by 369 ophthalmologists and followed for 24 months. Information on adverse events (AEs) was reported by the treating physician or detected by the data management team. Collected information included observed AE, AE start and end date, intensity, causal relationship, outcome, severity, suspected drug, and actions taken. Results. 2,687 AEs were reported for 1,176 of the 5,781 patients who had received a total of 32,621 injections: 27.4% nonserious AEs, 30.3% serious AEs, 27.3% nonserious adverse drug reactions (ADRs), and 15.0% serious ADRs. Most patients reported no AEs (79.7%) or only 1 AE (10.3%). AEs were most commonly reported in the Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) Eye disorders (9.4% of patients) and General disorders and administration site conditions (5.8%). The most frequent AEs by MedDRA preferred term (PT) were visual acuity reduced (3.5% of patients), intraocular pressure increased (2.5%), and drug ineffective (2.1%). AEs occurred most frequently after 3 or 4 injections (1,129 of 2,687 AEs). The proportion of AEs in the SOC Eye disorders decreased slightly with increasing number of injections, from 39.8% of events after 1 or 2 injections to 29.1% after 5 or more injections. Rates of the most frequently reported PTs did not show any consistent increase with increasing number of injections. A decrease in overall AE rates was observed over the study course. Conclusions. The results did not raise any new safety concerns for ranibizumab. The findings allow conclusions to be drawn on how pharmacovigilance data can be collected even more effectively in real-world studies to facilitate discussion on benefit-risk ratio.

scholarly journals Patients’ perceptions of visual impairment associated with smoking: A cross-sectional study of a United Kingdom tertiary eye centre

2021 ◽  
pp. 112067212110206
Author(s):  
Diya Baker ◽  
Onyinye Akpenyi ◽  
Haris Shahzad ◽  
Faye Mellington
Keyword(s):  
United Kingdom ◽  
Cross Sectional Study ◽  
Smoking Behaviour ◽  
Age Related Macular Degeneration ◽  
Health Campaigns ◽  
Cross Sectional ◽  
Adverse Health Effects ◽  
Established Risk Factor ◽  
Age Related ◽  
Eye Disorders

Smoking is a well-established risk factor for several eye disorders including cataracts and age-related macular degeneration. While many individuals are informed of the various adverse health effects, there is limited research into patients’ awareness of the relationship between smoking and eye disease and the potential impact this might have on reducing smoking behaviour. Our findings document the low level of awareness of the risk of blindness from smoking at a tertiary eye unit in the United Kingdom and highlight the need for increased involvement from eye care professionals, alongside health campaigns to educate the public of this consequence of smoking.

scholarly journals Istaroxime treatment ameliorates calcium dysregulation in a zebrafish model for Phospholamban R14del cardiomyopathy

2020 ◽  
Author(s):  
S.M. Kamel ◽  
C.J.M. van Opbergen ◽  
C.D. Koopman ◽  
A.O. Verkerk ◽  
Y. L. Onderwater ◽  
...  
Keyword(s):  
Structural Changes ◽  
Cellular Level ◽  
Zebrafish Model ◽  
Physiological Processes ◽  
Cardiac Contractile ◽  
Age Related ◽  
Intracellular Ca ◽  
Cardiac Contractile Dysfunction ◽  
Novel Drug

AbstractThe heterozygous phospholamban (PLN) p.Arg14del (R14del) mutation is found in patients with dilated or arrhythmogenic cardiomyopathy. The PLN R14del mutation triggers cardiac contractile dysfunction and arrhythmogenesis by affecting intracellular Ca2+ dynamics. Little is known about the physiological processes preceding PLN R14del induced cardiomyopathy, which is characterized by sub-epicardial accumulation of fibrofatty tissue, and a specific drug treatment is currently lacking. Here, we addressed these issues using a knock-in PLN R14del zebrafish model. Hearts from adult zebrafish with the R14del mutation display age-related remodeling with sub-epicardial inflammation and fibrosis. Echocardiography revealed contractile pulsus alternans before overt structural changes occurred, which correlated at the cellular level with action potential duration (APD) alternans. These functional alterations are preceded by diminished Ca2+ transient amplitudes in embryonic hearts. We found that istaroxime treatment ameliorates the in vivo Ca2+ dysregulation, rescues the cellular APD alternans, while it improves cardiac relaxation. Thus, we present novel insight into the pathophysiology of PLN R14del cardiomyopathy and identify istaroxime as a potential novel drug for its treatment.

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