Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images

PLoS Genetics, Journal Year: 2021, Volume and Issue: 17(5), P. e1009497 - e1009497

Published: May 12, 2021

Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose manage ophthalmic diseases including glaucoma. We present first large-scale genome-wide association study inner retinal morphology using phenotypes derived from OCT images 31,434 UK Biobank participants. identify 46 loci associated with thickness nerve fibre layer or ganglion cell plexiform layer. Only one these has been glaucoma, despite its clear role as a biomarker for disease, Mendelian randomisation does not support being on same genetic causal pathway extracted overall at fovea, representative foveal hypoplasia, which three SNPs were associated. additionally associate visual acuity. In contrast causes severe our results suggest spectrum in part genetically determined, consequences function.

Language: Английский

---

Comparison of Myopic Progression before, during, and after COVID-19 Lockdown

Ophthalmology, Journal Year: 2021, Volume and Issue: 128(11), P. 1655 - 1657

Published: March 23, 2021

Language: Английский

---

A large multiethnic GWAS meta-analysis of cataract identifies new risk loci and sex-specific effects

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: June 14, 2021

Cataract is the leading cause of blindness among elderly worldwide and cataract surgery one most common operations performed in United States. As genetic etiology formation remains unclear, we conducted a multiethnic genome-wide association meta-analysis, combining results from GERA UK Biobank cohorts, tested for replication 23andMe research cohort. We report 54 significant loci, 37 which were novel. Sex-stratified analyses identified CASP7 as an additional novel locus specific to women. show that genes within or near 80% cataract-associated loci are significantly expressed and/or enriched-expressed mouse lens across various spatiotemporal stages per iSyTE analysis. Furthermore, shows 32 candidate associated have altered gene expression 9 different perturbation models defects/cataract, suggesting their relevance biology. Our work provides further insight into complex architecture susceptibility.

Language: Английский

---

Candidate pathways for retina to scleral signaling in refractive eye growth

Experimental Eye Research, Journal Year: 2022, Volume and Issue: 219, P. 109071 - 109071

Published: April 18, 2022

The global prevalence of myopia, or nearsightedness, has increased at an alarming rate over the last few decades. An eye is myopic if incoming light focuses prior to reaching retinal photoreceptors, which indicates a mismatch in its shape and optical power. This commonly results from excessive axial elongation. Important drivers myopia epidemic include environmental factors, genetic their interactions, e.g., factors influencing effects factors. One factor often hypothesized be driver light, changed drastically rapidly on scale. In support this, it well established that size regulated by homeostatic process incorporates visual cues (emmetropization). allows detect minimize refractive errors quite accurately locally time modulating elongation via remodeling outermost coat, sclera. Critically, emmetropization not dependent post-retinal processing. Thus, appear influence through retina-to-sclera, retinoscleral, signaling cascade, capable transmitting information innermost layer layer. Despite significant research interest, specifics retinoscleral pathways remain elusive. While pharmacological treatments have proven effective slowing (most notably topical atropine), mechanisms behind these are still fully understood. Additionally, several neuromodulators, neurotransmitters, other small molecules been found length and/or error influenced myopigenic cues, yet little progress made explaining how signal originates retina crosses highly vascular choroid affect Here, we compile synthesize evidence surrounding three major candidate receiving attention - dopamine, retinoic acid, adenosine. All candidates both correlational causal backing involvement implicated multiple independent groups across diverse species. Two presented for retina-originating 1) all-trans acid 2) choroidal blood flow scleral oxygenation. Evidence crosstalk between discussed context two mechanisms.

Language: Английский

---

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus

Communications Biology, Journal Year: 2021, Volume and Issue: 4(1)

Published: March 1, 2021

Abstract Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children young adults a common indication for corneal transplantation worldwide. Here we report first large scale genome-wide association study keratoconus including 4,669 cases 116,547 controls. We have identified significant 36 genomic loci that, time, implicate both dysregulation collagen matrix integrity cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, some disease shared other diseases, such Fuchs endothelial dystrophy. variants associated explain 12.5% genetic variance, which shows potential future development diagnostic test detect susceptibility disease.

Language: Английский

---

Short Chain Fatty Acid Metabolism in Relation to Gut Microbiota and Genetic Variability

Nutrients, Journal Year: 2022, Volume and Issue: 14(24), P. 5361 - 5361

Published: Dec. 16, 2022

It is widely accepted that the gut microbiota plays a significant role in modulating inflammatory and immune responses of their host. In recent years, host-microbiota interface has gained relevance understanding development many non-communicable chronic conditions, including cardiovascular disease, cancer, autoimmunity neurodegeneration. Importantly, dietary fibre (DF) associated compounds digested by resulting metabolites, especially short-chain fatty acids (SCFA), were significantly with health beneficial effects, such as via proposed anti-inflammatory mechanisms. However, SCFA metabolic pathways are not fully understood. Major steps include production microbiota, uptake colonic epithelium, first-pass effects at liver, followed biodistribution metabolism host's cellular level. As patterns do affect all individuals equally, host genetic makeup may play fate these addition to other factors might influence age, birth through caesarean, medication intake, alcohol tobacco consumption, pathogen exposure physical activity. this article, we review DF, from intake intracellular fibre-derived products, identify possible sources inter-individual variability related variation. Such be indicative phenotypic flexibility response diet, predictive long-term adaptations factors, maladaptation tissue damage, which develop into disease specific predispositions, thus allowing for better prediction potential following personalized intervention DF.

Language: Английский

---

Myopia prediction: a systematic review

Eye, Journal Year: 2021, Volume and Issue: 36(5), P. 921 - 929

Published: Oct. 13, 2021

Language: Английский

---

Prevalence and Risk Factors of Myopia in Young Adults: Review of Findings From the Raine Study

Frontiers in Public Health, Journal Year: 2022, Volume and Issue: 10

Published: April 27, 2022

Myopia tends to develop and progress fastest during childhood, the age of stabilization has been reported be 15–16 years old. Thus, most studies on myopia have centered children. Data refractive error profile in young adulthood — a time life when is thought stabilized unaffected by age-related pathology such as cataract are limited. The Raine Study following community-based cohort adults representative general Western Australia population since their prenatal periods 1989–1991, with eye examinations performed participants were 20 28 At old, prevalence was 25.8%. Using long-term trajectory serum vitamin D levels conjunctival ultraviolet autofluorescence (CUVAF) area objectively quantify sun exposure, confirmed negative relationship between spent outdoors prevalence. However, prospective required determine amount CUVAF or associated duration. Combining data from several other cohorts, Mendelian randomization link genetic predisposition toward higher education. Several novel potential associations ocular biometry investigated, including fetal growth trajectory, which found significantly corneal curvature at years. By 28, had increased 33.2%. Between progressed axial length elongated, average, −0.041D/year 0.02 mm/year, respectively. Smaller follow-up, female sex, parental significant risk factors for incidence progression Given limited research adults, further investigations warranted confirm findings, well identify environmental this group.

Language: Английский

---

Ocular Nanomedicine

Advanced Science, Journal Year: 2022, Volume and Issue: 9(15)

Published: Feb. 12, 2022

Abstract Intrinsic shortcomings associated with conventional therapeutic strategies often compromise treatment efficacy in clinical ophthalmology, prompting the rapid development of versatile alternatives for satisfactory diagnostics and therapeutics. Given advances material science, nanochemistry, nanobiotechnology, a broad spectrum functional nanosystems has been explored to satisfy extensive requirements ophthalmologic applications. In present review, recent progress nanosystems, both emerging nanomaterials ophthalmology from state‐of‐the‐art studies, are comprehensively examined role their fundamental physicochemical properties bioavailability, tissue penetration, biodistribution, elimination after interacting microenvironment emphasized. Furthermore, along surface engineering nanomaterials, theranostic methodologies promoted as potential multipurpose ocular applications, such biomimetic (e.g., smart electrochemical eye), thus provoking holistic review “ocular nanomedicine.” By affording insight into challenges encountered by nanomedicine further highlighting direction future this provides an incentive enriching nanomedicine‐based research translation.

Language: Английский

---

Mendelian Randomization Implicates Bidirectional Association between Myopia and Primary Open-Angle Glaucoma or Intraocular Pressure

Ophthalmology, Journal Year: 2022, Volume and Issue: 130(4), P. 394 - 403

Published: Dec. 6, 2022

Language: Английский

---