Myopia (short-sightedness) and hyperopia (long-sightedness) occur when the eye grows too long or short, respectively, for its refractive power. There are currently approximately 1.45 billion myopes worldwide and prevalence is rising dramatically. Although high myopia significantly increases the risk of developing a range of sight-threatening disorders, the molecular mechanisms underlying ocular growth regulation and its relationship to these secondary complications remain poorly understood. Thus, this study meta-analyzed transcriptome datasets collected in the commonly used chick model of optically-induced refractive error. Fifteen datasets (collected across five previous studies) were obtained from GEO, preprocessed in Bioconductor, and divided into 4 conditions representing early (≤1 day) and late (>1 day) myopia and hyperopia induction. Differentially expressed genes in each condition were then identified using Rank Product meta-analysis. The results provide novel evidence for transcriptional activation of the complement system during both myopia and hyperopia induction, and confirm existing literature implicating cell signaling, mitochondrial, and structural processes in refractive error. Further comparisons demonstrated that the meta-analysis results also significantly improve concordance with broader omics data types (i.e., human genetic association and animal proteomics studies) relative to previous transcriptome studies, and show extensive similarities with the genes linked to age-related macular degeneration, choroidal neovascularization, and cataract.

Myopia (short-sightedness) affects 1.45 billion people worldwide, many of whom will develop sight-threatening secondary disorders. Myopic eyes are characterized by excessive size while hyperopic (long-sighted) eyes are typically small. The biological and genetic mechanisms underpinning the retina’s local control of these growth patterns remain unclear. In the present study, we used RNA sequencing to examine gene expression in the retina/RPE/choroid across 3 days of optically-induced myopia and hyperopia induction in chick. Data were analysed for differential expression of single genes, and Gene Set Enrichment Analysis (GSEA) was used to identify gene sets correlated with ocular axial length and refraction across lens groups. Like previous studies, we found few single genes that were differentially-expressed in a sign-of-defocus dependent manner (only BMP2 at 1 day). Using GSEA, however, we are the first to show that more subtle shifts in structural, metabolic, and immune pathway expression are correlated with the eye size and refractive changes induced by lens defocus. Our findings link gene expression with the morphological characteristics of refractive error, and suggest that physiological stress arising from metabolic and inflammatory pathway activation could increase the vulnerability of myopic eyes to secondary pathologies

Environmental light entrains many physiological and behavioural processes to the 24 h solar cycle. Such light-driven circadian rhythms are centrally controlled by the suprachiasmatic nucleus (SCN), which receives information from the short-wavelength-sensitive intrinsically photosensitive retinal ganglion cells. The SCN synchronizes local clocks throughout the body affecting sleep/wake routines and the secretion of neuroendocrine-linked hormones such as melatonin from the pineal gland and cortisol via the hypothalamic pituitary adrenal (HPA) axis. Although the effects of light parameters on melatonin have been recently reviewed, whether the experimental variation of the spectral power distribution and intensity of light can induce changes in cortisol rhythms remains unclear. Thus, this systematic review evaluated the effects of daytime exposure to lights of different spectral wavelength characteristics and luminance intensity on the cortisol levels in healthy individuals. A search of the PubMed, Web of Science, EMBASE, CINAHL, Medline, PsycINFO and Cochrane Library databases on 19 June 2023 identified 3418 articles, of which 12 studies (profiling 337 participants) met the inclusion and risk of bias criteria. An analysis of the literature indicated that exposure to bright lights of any colour during the late night or early morning can induce significant increases in cortisol secretion relative to time-matched dim light comparison conditions. Furthermore, exposure to bright lights with stronger short-wavelength (blue/green) components in the early morning typically induced greater increases in cortisol relative to lights with stronger long-wavelength (red) components. Thus, the circadian regulation of cortisol is sensitive to the wavelength composition of environmental lighting, in line with the more commonly studied melatonin. As such, wavelength characteristics should be optimized and reported in light intervention studies (particularly for the investigation of cortisol-associated disorders and HPA axis function), and exposure to short-wavelength light during sensitive periods should be carefully considered in constructed environments (e.g., bedroom and classroom lighting and device screens).

Purpose: RNA sequencing analysis has demonstrated bidirectional changes in metabolism, structural and immune pathways during early induction of defocus induced myopia. Thus, the aim of this study was to investigate whether similar gene pathways are also related to the more excessive axial growth, ultrastructural and elemental microanalytic changes seen during the induction and recovery from form-deprivation myopia (FDM) in chicks and predicted by the RIDE model of myopia. Methods: Archived genomic transcriptome data from the first three days of induction of monocularly occluded form deprived myopia (FDMI) in chicks was obtained from the GEO database (accession # GSE6543) while data from chicks monocularly occluded for 10 days and then given up to 24 h of normal visual recovery (FDMR) were collected. Gene set enrichment analysis (GSEA) software was used to determine enriched pathways during the induction (FDMI) and recovery (FDMR) from FD. Curated gene-sets were obtained from open access sources. Results: Clusters of significant changes in mitochondrial energy metabolism, neurotransmission, ion channel transport, G protein coupled receptor signalling, complement cascades and neuron structure and growth were identified during the 10 days of induction of profound myopia and were found to correlate well with change in axial dimensions. Bile acid and bile salt metabolism pathways (cholesterol/lipid metabolism and sodium channel activation) were significantly upregulated during the first 24 h of recovery from 10 days of FDM. Conclusions: The gene pathways altered during induction of FDM are similar to those reported in defocus induced myopia and are established indicators of oxidative stress, osmoregulatory and associated structural changes. These findings are also consistent with the choroidal thinning, axial elongation and hyperosmotic ion distribution patterns across the retina and choroid previously reported in FDM and predicted by RIDE.

Purpose: To identify commonalities between the genes in close proximity to genome-wide association study (GWAS) refractive error and axial length loci, and the genes and proteins differentially expressed in animal models of optically induced refractive error. Methods: The GWAS catalog was searched for loci significantly (P ≤ 5*10⁻⁸) associated with refractive error or axial length. PubMed was searched for exploratory animal transcriptome and proteomics studies of optically induced refractive error. A total of 15 GWAS, 7 transcriptome, and 9 proteomics studies met inclusion criteria. Ensembl's BioMart was used to identify human orthologs for the differentially expressed genes and proteins from animal studies. These orthologs were then compared to the protein-coding genes within 1 megabase (Mb), 500 kilobases (kb), and 250 kb of human GWAS loci by using the GeneOverlap R package, and Benjamini-Hochberg–adjusted P values and odds ratios (ORs) were calculated for each intersection. Results: The genes near human GWAS loci overlapped significantly with the genes downregulated during early myopia induction in animals (1Mb: OR = 1.56, P = 0.025; 500 kb: OR = 1.92, P = 0.010; 250 kb: OR = 2.33, P = 0.010). There was also significant overlap between the genes and proteins differentially expressed in late myopia (OR = 4.12, P = 0.018). When animal study results were segregated by methodologic parameters, GWAS candidate genes overlapped significantly with the genes differentially expressed at early (OR = 1.50, P = 0.010) but not late (OR = 1.04, P = 0.684) induction time-points. Gene and protein expression responses also appeared well conserved across model species, and there was no evidence of greater GWAS–transcriptome concordance in similar species to humans (e.g., primates or mammals). Conclusions: These findings suggest that genetic and environmental factors control ocular growth via similar biological pathways across species, and support the continued use of animal models for investigating the biological mechanisms underlying human myopia development.

Migraine is a leading cause of disability in young adults. It occurs more frequently in females, often comorbidly with stress disorders, suggesting an association with hypothalamic sex and stress hormonal function and a likely interaction with autonomic nervous system activation. Thus, this study aimed to meta‐analyse current literature pertaining to female and male sex hormones (estrogen, progesterone and testosterone concentration), hypothalamic–pituitary–adrenal axis (HPA axis) cortisol responses and heart rate variability (HRV) in migraineurs and controls aged 13–65 years. A systematic search of MEDLINE, Embase, PsycINFO, PubMed, CINAHL and Web of Science databases on 29/08/2022 identified 29 studies for meta‐analysis (encompassing 719 migraineur and 592 control participants) that met inclusion and NHLBI risk of bias criteria. Results demonstrated that estrogen concentrations of female migraineurs were reduced (g = −.60, 95% CI [−.91, −.29], p < .001) in the luteal phase of the menstrual cycle, compared to controls. No differences were found in progesterone levels overall in female migraineurs, nor in testosterone levels in male migraineurs compared to controls. Further, early diurnal cortisol concentrations were elevated (g = .32, 95% CI [.00, .63], p = .036) in female and male migraineurs compared to controls, though no differences were found in HRV of female or male migraineurs compared to controls. These findings of dysregulation of estrogen in females and cortisol dysregulation in female and male migraineurs indicate perturbed hypothalamic function and highlight the association of migraine with stress and the need for further rigorous investigation of hypothalamic neuroendocrine functions in migraineurs of both sexes.