Transcriptomic and Proteomic Analyses of Sclera in Lens-Induced Myopic Guinea Pigs
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ABSTRACT:
ORGANISM(S): Cavia porcellus
PROVIDER: GSE280609 | GEO | 2025/02/25
REPOSITORIES: GEO
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Project description:BackgroundMyopia development is commonly assessed by an increase in axial length, which may lead to high myopia and visual impairment. This study aims to identify potential biomarkers and signaling pathways in the sclera during experimental axial elongation.MethodsA myopia guinea pig model was established using male guinea pigs aged 2-3 weeks, which underwent bilateral lens-induced myopization (LIM) (study group) or were left untreated (control group). An integrated analysis of transcriptomic and proteomic was performed to identify differentially expressed genes (DEGs) in the sclera. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the DEGs related signaling pathways. Promising candidate markers were further tested by Western blot analysis. Transmission electron microscopy was used to assess scleral fiber changes in myopic guinea pigs.ResultsDuring the study period, axial elongation was significantly greater in the study group (0.59 ± 0.05 mm vs. 0.47 ± 0.02 mm; P < 0.001), accompanied by a reduction in the thickness of the retina (121.9 ± 2.50 μm vs. 134.6 ± 0.48 μm; P < 0.001), choroid (38 ± 1.0 μm vs. 50 ± 0.8 μm; P < 0.001), and sclera (100.8 ± 2.78 μm vs. 155.6 ± 4.78 μm; P < 0.001). Integrated transcriptomic and proteomic analyses identified 34 upregulated genes, with significant activation and enrichment of the circadian rhythm pathway. Among the top enriched pathways, key differentially expressed genes included retinoid-related orphan receptors RORα and RORβ, which are recognized as critical signals modulating the scleral hypoxia response. Western blot analysis confirmed upregulation of RORα, RORβ, melatonin receptor type 1 (MT1), and HIF-1α in the sclera, while melatonin receptor type 2 (MT2) expression remained unchanged between the groups. Transmission electron microscopy revealed a significantly higher proportion of thin collagen fibers compared to thick fibers in the LIM group (P < 0.05).ConclusionsAxial elongation-related remodeling of scleral collagen is closely linked to circadian rhythm and hypoxia pathways, with RORα, RORβ, melatonin receptors, and HIF-1α identified as potential key regulators. Additionally, scleral fiber size decreases progressively with scleral remodeling in myopia development.
| S-EPMC11905693 | biostudies-literature
Project description:Transcriptomic and Proteomic Analyses of Sclera in Lens-Induced Myopic Guinea Pigs
| PRJNA1179481 | ENA
Project description:Biomechanical changes in the sclera likely underlie the excessive eye elongation of axial myopia. We studied the biomechanical characteristics of myopic sclera at the microscopic level using scanning acoustic microscopy (SAM) with 7-μm in-plane resolution. Guinea pigs underwent form-deprivation (FD) in one eye from 4 to 12 days of age to induce myopia, and 12-μm-thick scleral cryosections were scanned using a custom-made SAM. Two-dimensional maps of the bulk modulus (K) and mass density (ρ) were derived from the SAM data using a frequency-domain approach. We assessed the effect on K and ρ exerted by: 1) level of induced myopia, 2) region (superior, inferior, nasal or temporal) and 3) eccentricity from the nerve using univariate and multivariate regression analyses. Induced myopia ranged between -3D and -9.3D (Mean intraocular difference of -6.2 ± 1.7D, N = 11). K decreased by 0.036 GPa for every 1.0 D increase in induced myopia across vertical sections (p < 0.001). Among induced myopia right eyes, K values in the inherently more myopic superior region were 0.088 GPa less than the inferior region (p = 0.002) and K in the proximal nasal region containing the central axis were 0.10 GPa less than temporal K (p = 0.036). K also increased 0.12 GPa for every 1 mm increase in superior vertical distance (p < 0.001), an effect that was blunted after 1 week of FD. Overall, trends for ρ were less apparent than for K. ρ values increased by 20.7 mg/cm3 for every 1.00 D increase in induced myopia across horizontal sections (p < 0.001), and were greatest in the region containing the central posterior pole. ρ values in the inherently more myopic superior region were 13.1 mg/cm3 greater than that found in inferior regions among control eyes (p = 0.002), and increased by 11.2 mg/cm3 for every 1 mm increase in vertical distance (p = 0.001). This peripheral increase in ρ was blunted after 1 week of FD. Scleral material properties vary depending on the location in the sclera and the level of induced myopia. Bulk modulus was most reduced in the most myopic regions (both induced myopia and inherent regional myopia), and suggests that FD causes microscopic local decreases in sclera stiffness, while scleral mass density was most increased in the most myopic regions.
| S-EPMC6712578 | biostudies-literature
Project description:This study aims to verify the involvement of scleral endoplasmic reticulum stress (ERS) in form-deprived myopia (FDM) model of guinea pigs, investigate the therapeutic effects of quercetin (Qcn) on FDM as well as explore the underlying mechanisms in human scleral fibroblast (HSF).
2025-01-02 | GSE285669 | GEO
Project description:The sclera is the target organ of axial elongation during myopia onset and progression. Visualizing the sclera in-vivo is important for monitoring the dynamic changes of the sclera remodeling in experimental myopia. In the present study, three-week-old tricolor guinea pigs were subjected to negative controls (n = 8), monocular negative lens-induced myopia (LIM, n = 10), or combining monocular LIM and intravitreally mTORC1 agonist (MHY1485, 4 µg) injection for inducing high myopia (LIM + MHY1485 group, n = 10) for four weeks. Serial biometric measurements were performed to monitor experimental myopia onset and progression. Swept-source optical coherence tomography (SS-OCT) was performed to measure sclera thickness at the beginning and end of study. The results showed four weeks of LIM and LIM + MHY1485 induced a significant degree of myopia shift, compared to the negative control (Control, -2.04 ± 0.60; LIM - 6.21 ± 0.55; LIM + MHY1485, -9.14 ± 1.11, diopters, P < 0.0001). The cross-sectional SS-OCT showed clear boundaries of the inner and outer boundaries of the sclera. At baseline, the mean sclera thickness was 105.05 ± 5.41 μm. At the end of the study, sclera thickness significantly correlated with axial length (coefficient = -4.49 μm for every 0.1 mm axial length increase, 95%CI: -3.56 to -5.83 μm, P < 0.001) and refractive error (coefficient = -2.77 μm for every 1 diopter myopic shift, 95%CI: -2.06 to -3.47 μm, P < 0.001) among all guinea pigs. Sclera thickness also significantly correlates with choroidal thickness and choroidal vascularity index (%). In conclusion, the present study shows SS-OCT can be used as a non-invasive method to evaluate sclera thickness and monitor myopia progression in the guinea pig model of LIM.
| S-EPMC11874840 | biostudies-literature
Project description:The sclera maintains and protects the eye ball, which receives visual inputs. The aim of this study is to identify characteristics of the human sclera as one of the connective tissues derived from the neural crest and mesoderm. We have here demonstrated microarray data of cultured human scleral cells. Keywords: sclera, cartilage
2008-04-10 | GSE10934 | GEO
Project description:The pathogenesis of myopia involves different molecular mechanisms and pathways, which can be reflected in the aqueous humor. In our study, aqueous humor was collected for liquid chromatograph mass spectrometer (LC/MS) analysis from 30 individual eyes that underwent phacoemulsification and intraocular lens (IOL) implantation. A total of 190 DEPs (differentially expressed proteins) were identified, which revealed their involvement in pathways such as carbon metabolism, lipid, and cholesterol metabolism, ECM (extracellular matrix) component regulation, and scleral remodeling in the context of high myopia. Further analysis revealed 15 interacting hub proteins, encompassing functions related to lipoprotein assembly, regulation, complement cascades, and fibrin formation. Subsequent validation demonstrated elevated levels of APOE (apolipoprotein E), C3 (complement 3), and AHSG (alpha-2-HS-glycoprotein) in the high myopia group (31 eyes of cataracts and 45 eyes of high myopia with cataracts), while AHSG had a significant positive correlation with axial length in patients with high myopia and good efficacy in distinguishing between myopic and non-myopic groups. These results suggested that the interaction of lipoproteins, complement cascades, and the fibrinolytic system played a pivotal role in the pathological process of myopia, while the metabolism of essential materials and the remodeling of ECM and tissue structure were affected in the eyes of individuals with high myopia.
2024-05-23 | PXD047584 | Pride
Project description:KCNQ5 is suggestively associated with myopia, but its specific role in the myopic process has not been studied further. The aim of this study was to investigate the expression of potassium channel gene KCNQ5 and the changes of K+ microenvironment within the retina of form deprivation myopia (FDM) guinea pigs. A total of 60 guinea pigs were randomly divided into the normal control (NC) group, the self-control (SC) group, and the form-deprivation (FD) group for different treatments. Molecular assays and immunohistochemistry (IHC) were conducted to measure the expression and distribution of KCNQ5-related gene and protein in the retina. We determined the K+ concentration in the retina. In addition, the possible effects of form deprivation on potassium ionic currents and the pharmacological sensitivity of KCNQ5 activator Retigabine and inhibitor XE991 to the M-current in RPE cells were investigated using the patch-clamp technique. As a result, FD eyes exhibited more myopic refraction and longer AL. The mRNA and protein levels of KCNQ5 significantly decreased in the FD eyes, but the K+ concentration increased. In addition, the M-type K+ current [IK(M)] density decreased in FD RPE cells, and were activated or inhibited in a concentration-dependent manner due to the addition of Retigabine or XE991. Overall, KCNQ5 was significantly downregulated in the retina of FD guinea pigs, which may be associated with the increasing K+ concentration, decreasing IK(M) density, and elongating ocular axis. It suggested that KCNQ5 may play a role in the process of myopia, and the intervention of potassium channels may contribute to the prevention and control of myopia.
| S-EPMC8733613 | biostudies-literature
Project description:Microarray study comparing the trabecular meshwork (TM) with TM-MSC, corneal and scleral tissues
2017-06-09 | GSE87526 | GEO
Project description:PurposeBright light conditions are supposed to curb eye growth in animals with experimental myopia. Here we investigated the effects of temporal bright light at very low frequencies exposures on lens-induced myopia (LIM) progression.MethodsMyopia was induced by application of -6.00 D lenses over the right eye of guinea pigs. They were randomly divided into four groups based on exposure to different lighting conditions: constant low illumination (CLI; 300 lux), constant high illumination (CHI; 8,000 lux), very low frequency light (vLFL; 300/8,000 lux, 10 min/c), and low frequency light (LFL; 300/8,000 lux, 20 s/c). Refraction and ocular dimensions were measured per week. Changes in ocular dimensions and refractions were analyzed by paired t-tests, and differences among the groups were analyzed by one-way ANOVA.ResultsSignificant myopic shifts in refractive error were induced in lens-treated eyes compared with contralateral eyes in all groups after 3 weeks (all P < 0.05). Both CHI and LFL conditions exhibited a significantly less refractive shift of LIM eyes than CLI and vLFL conditions (P < 0.05). However, only LFL conditions showed significantly less overall myopic shift and axial elongation than CLI and vLFL conditions (both P < 0.05). The decrease in refractive error of both eyes correlated significantly with axial elongation in all groups (P < 0.001), except contralateral eyes in the CHI group (P = 0.231). LFL condition significantly slacked lens thickening in the contralateral eyes.ConclusionsTemporal bright light at low temporal frequency (0.05 Hz) appears to effectively inhibit LIM progression. Further research is needed to determine the safety and the potential mechanism of temporal bright light in myopic progression.
| S-EPMC10655705 | biostudies-literature