Candidate pathways for retina to scleral signaling in refractive eye growth

Experimental Eye Research, Год журнала: 2022, Номер 219, С. 109071 - 109071

Опубликована: Апрель 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.

Язык: Английский

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Studies of all-transretinoic acid transport in myopigenesis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 4, 2025

Abstract Purpose Myopia incidence is increasing globally. All- trans retinoic acid (atRA) important in myopigenic retinoscleral signaling, motivating research on its ocular transport. However, atRA’s weak autofluorescence limits direct visualization tissues. Further, atRA hydrophobic and must bind to protein carriers for We assessed a fluorescent analog of (LightOx TM 14, CAS:198696-03-6, referred as ‘floRA’), an experimentally accessible surrogate by: (i) evaluating binding carrier proteins (ii) visualizing distribution Methods Binding atRA-carrier using fluorescence quenching assays with bovine serum albumin (BSA), high density lipoprotein (HDL), apolipoprotein A-I (Apo A-I) retinol 4 (RBP4). Direct Wild-type C57BL/6J mice were euthanized, eyes enucleated, wedges containing sclera choroid incubated specific durations 50 μM floRA+BSA. The wedge centers cryo-sectioned counterstained nuclei. Fluorescent micrographs acquired analyzed ImageJ. Results Association constants (K ) floRA similar ranged from 2-13 × 10 5 M -1 , indicating non-specific binding. could be visualized choroid, yet showed significant spatial heterogeneity (enhanced often colocalizing nuclei). Conclusions reasonable BSA, HDL, Apo RBP4. Considering these proteins’ relative extravascular abundances, their affinity atRA, we predict that carrier. Use whole tissue tracer studies shows promise but requires further refinement.

Язык: Английский

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Insights into Myopia from Mouse Models

Annual Review of Vision Science, Год журнала: 2024, Номер 10(1), С. 213 - 238

Опубликована: Апрель 18, 2024

Animal models are critical for understanding the initiation and progression of myopia, a refractive condition that causes blurred distance vision. The prevalence myopia is rapidly increasing worldwide, increases risk developing potentially blinding diseases. Current pharmacological, optical, environmental interventions attenuate in children, but it still unclear how this occurs or these can be improved to increase their protective effects. To optimize interventions, directed mechanistic studies needed. mouse model well-suited because its well-characterized visual system genetic experimental tools available, which combined with pharmacological manipulations powerful investigations causation. This review describes aspects support use as presents genetic, significantly contribute our mechanisms underlie myopigenesis.

Язык: Английский

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Meta-analysis of retinal transcriptome profiling studies in animal models of myopia

Frontiers in Medicine, Год журнала: 2025, Номер 11

Опубликована: Янв. 14, 2025

Objective Myopia prevalence is increasing at alarming rates, yet the underlying mechanistic causes are not understood. Several studies have employed experimental animal models of myopia and transcriptome profiling to identify genes pathways contributing myopia. In this study, we determined retinal changes in response form deprivation mouse retinas. We then conducted a meta-analysis incorporating all publicly available datasets analyzed how results related associated with refractive errors human genome-wide association (GWAS). Methods Form was induced three male C57BL6/J mice from postnatal day 28 (P28) P42. Retinal gene expression RNA sequencing, followed by differential analysis DESeq2 identification Kyoto Encyclopedia Genes Genomes (KEGG). A systematic search identified four similar transcriptomics using chicks or mice. The five underwent meta-analyses determine pathways. were compared Results Differential form-deprived retinas revealed 235 significantly altered transcripts, implicating BMP2 signaling pathway circadian rhythms, among others. Transcriptome-wide found 427 differentially expressed model 1,110 chick model, limited overlap between species. Pathway these two sets implicated TGF-beta rhythm both Some only included dopamine HIF-1 pathway, whereas glucagon follistatin changed has also been entrainment processes mice, chicks, humans. Conclusion This study highlights power combining enhance statistical robust across different conditions. data supports other evidence that rhythms involved myopic eye growth.

Язык: Английский

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Color vision-associated environmental and biological factors in the development of myopia

Experimental Eye Research, Год журнала: 2025, Номер 254, С. 110324 - 110324

Опубликована: Март 7, 2025

Язык: Английский

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Modulation of All-Trans Retinoic Acid by Light and Dopamine in the Murine Eye

Investigative Ophthalmology & Visual Science, Год журнала: 2025, Номер 66(3), С. 37 - 37

Опубликована: Март 18, 2025

Purpose: Ambient light exposure is linked to myopia development in children and affects susceptibility animal models. Currently, it unclear which signals mediate the effects of on myopia. All-trans retinoic acid (atRA) dopamine (DA) oppositely influence experimental may be involved retinoscleral signaling cascade underlying myopic eye growth. However, how ocular atRA responds different lighting whether DA interact remains unknown. Methods: Dark-adapted C57BL/6J mice (29–31 days old) were exposed dim (1 lux), mid (59 or bright (12,000 lux) ambient for 5 60 minutes. Some also systemically administered precursor, LDOPA, before exposure. After exposure, retina back (BOE) collected analyzed levels atRA, DA, metabolite, DOPAC. Results: turnover (DOPAC/DA ratio) increased magnitude after only minutes higher luminance, but was minimal BOE. In contrast, BOE significantly decreased with luminance longer duration Intriguingly, LDOPA-treated had a transient reduction retinal compared saline-treated mice, whereas treatment no effect DA. Conclusions: Ocular affected by lighting, Overall, these data suggest specific interactions between that could have implications

Язык: Английский

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Research Advances in Methods for the Prevention and Control of Myopia

Advances in Clinical Medicine, Год журнала: 2025, Номер 15(04), С. 3010 - 3016

Опубликована: Янв. 1, 2025

Язык: Английский

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Distinct Transcriptomic Profiles of Cultured Anterior and Posterior Populations of Human Infant Scleral Fibroblasts: Including Dopamine Receptors

Investigative Ophthalmology & Visual Science, Год журнала: 2025, Номер 66(5), С. 29 - 29

Опубликована: Май 22, 2025

The transcriptomic profiling of scleral fibroblasts remains largely unexplored. To elucidate their heterogeneity, we performed single-cell RNA sequencing (scRNA-seq) on primary infant fibroblasts. Primary fibroblasts, cultured at passage 2 from the anterior, equatorial, and posterior regions sclera (3 months to years age) were subjected scRNA-seq using 10x Genomics platform. In-depth analysis revealed distinct profiles between anterior including differential expression dopamine (DA) receptors, which was subsequently validated both in vitro situ. Furthermore, regulatory role DA remodeling assessed an collagen gel contraction assay, involvement receptor activity this process further explored through pharmacological manipulation gene silencing approaches. Infant have subpopulations, each exhibiting profiles. Anterior show increased D1-like but exhibit elevated D2-like receptors. enhances inhibitory effect sclera, whereas activity, particularly that DRD2 counteracts effect. Gene DRD4 significantly DA-mediated inhibition sclera. our knowledge, study presents first comprehensive revealing heterogeneity. investigation fibroblast provides new insights into how signaling modulates remodeling.

Язык: Английский

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The Role of Scleral Changes in the Progression of Myopia: A Review and Future Directions

Clinical ophthalmology, Год журнала: 2025, Номер Volume 19, С. 1699 - 1707

Опубликована: Май 1, 2025

This review article comprehensively examines the alterations in scleral collagen fibers and extracellular matrix (ECM) during myopia progression, with a particular focus on hypoxia theory inflammatory mechanisms. It delves into key signaling pathways, including metalloproteinase - 2 (MMP-2) pathway, inducible factors (HIF-1α HIF-2α) Wnt pathway. By elucidating intricate relationships between these this highlights latest advancements prevention control strategies that target sclera. Moreover, it provides novel insights molecular mechanisms underlying remodeling explores their potential therapeutic applications for effectively managing progression.

Язык: Английский

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Animal modeling for myopia

Advances in Ophthalmology Practice and Research, Год журнала: 2024, Номер 4(4), С. 173 - 181

Опубликована: Июнь 5, 2024

Myopia is one of the most common eye diseases globally, and has become an increasingly serious health concern among adolescents. Understanding factors contributing to onset myopia strategies slow its progression critical reducing prevalence.

Язык: Английский

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