ABSTRACT
Purpose: This study aims to investigate the impact of axial elongation on ganglion cell complex thickness (GCCT) and retinal capillary density (CD) using wide-field swept-source optical coherence tomography angiography. Methods: A retrospective cross-sectional analysis was conducted involving 506 eyes. Fovea-centered scans were obtained to assess the subregional GCCT and capillary density across the whole retina, the superficial capillary plexus (SCP), and deep capillary plexus (DCP) among three groups: normal control, high myopia (HM) eyes with axial length < 28 mm, and HM eyes with axial length > 28 mm. Regional variations (central vs. peripheral, quadrants difference [superior, inferior, nasal, and temporal]) were analyzed. Results: In HM eyes with axial length > 28 mm, GCCT and retinal CD exhibit a general decline in most regions (P < 0.05). In HM eyes with axial length < 28 mm, significant reductions were observed specifically in peripheral regions, as in the GCCT beyond the 3 × 3 mm2 area and CD in the 9-12 mm whole retina, 9-12 mm superior SCP, and 6-12 mm DCP (P < 0.05). Maximum GCCT and retinal CD reduction with axial elongation was observed in subregions beyond 6 × 6 mm2. Conclusions: GCCT beyond the 3 × 3 mm2 area and peripheral retinal CD beyond the 6 × 6 mm2 area were more susceptible to axial elongation and are thereby deserving of particular attention. Translational Relevance: It is necessary to evaluate different regions during the clinical assessment of the effect of myopia on the fundus and pay close attention to the peripheral retina.
Subject(s)
Retinal Ganglion Cells , Retinal Vessels , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Cross-Sectional Studies , Retrospective Studies , Male , Retinal Ganglion Cells/pathology , Female , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Middle Aged , Adult , Myopia/pathology , Myopia/diagnostic imaging , Myopia/physiopathology , Microvessels/pathology , Microvessels/diagnostic imaging , Axial Length, Eye/pathology , Axial Length, Eye/diagnostic imaging , Nerve Fibers/pathology , Fluorescein Angiography/methods , Young Adult , Aged , Capillaries/pathology , Capillaries/diagnostic imagingABSTRACT
Extreme myopia (EM), defined as a spherical equivalent (SE) ≤ -10.00 diopters (D), is one of the leading causes of sight impairment. Known EM-associated variants only explain limited risk and are inadequate for clinical decision-making. To discover risk genes, we performed a whole-exome sequencing (WES) on 449 EM individuals and 9606 controls. We find a significant excess of rare protein-truncating variants (PTVs) in EM cases, enriched in the retrograde vesicle-mediated transport pathway. Employing single-cell RNA-sequencing (scRNA-seq) and a single-cell polygenic burden score (scPBS), we pinpointed PI16 + /SFRP4+ fibroblasts as the most relevant cell type. We observed that KDELR3 is highly expressed in scleral fibroblast and involved in scleral extracellular matrix (ECM) organization. The zebrafish model revealed that kdelr3 downregulation leads to elongated ocular axial length and increased lens diameter. Together, our study provides insight into the genetics of EM in humans and highlights KDELR3's role in EM pathogenesis.
Subject(s)
Exome Sequencing , Mutation , Zebrafish , Humans , Animals , Zebrafish/genetics , Male , Female , Fibroblasts/metabolism , Exome/genetics , Genome-Wide Association Study , Adult , Myopia/genetics , Myopia/metabolism , Myopia/pathology , Sclera/metabolism , Sclera/pathology , Extracellular Matrix/metabolism , Extracellular Matrix/genetics , Genetic Predisposition to Disease , Single-Cell Analysis , Case-Control Studies , Child , Young AdultABSTRACT
To analyze the relationship in retinal thickness, macula retina and choroidal microcirculation in pediatric patients with myopia. Pediatric patients with high myopia (high myopia group, nâ =â 30, 60 eyes) and pediatric patients with low to moderate myopia (low myopia group, nâ =â 30, 60 eyes) admitted to our hospital from January 2021 to January 2022 were randomly selected as the study subjects. Retinal thickness, the blood density of retina, and the blood density of the choroid were collected in each area of the macula by taking optical coherence tomography (OCT) and OCT angiography (OCTA). Pearson correlation analysis was conducted to compare the results from the 2 groups. Outer retinal thickness showed a weak positive correlation with Superficial vascular complex flow density (SVD) and deep vascular complex flow density (DVD) (Pâ <â .05), but no significant correlation with choroidal capillary density (Pâ >â .05); inner retinal thickness showed a weak positive correlation with SVD and DVD (Pâ <â .05), but no significant correlation with choroidal capillary density (Pâ >â .05). In pediatric patients with myopia, there is a positive correlation between the blood flow density of macular retina and retinal thickness, and the retinal thickness will become thinner with increasing myopia.
Subject(s)
Choroid , Macula Lutea , Microcirculation , Myopia , Retina , Tomography, Optical Coherence , Humans , Child , Male , Female , Choroid/blood supply , Choroid/diagnostic imaging , Choroid/pathology , Myopia/physiopathology , Myopia/pathology , Myopia/diagnostic imaging , Microcirculation/physiology , Tomography, Optical Coherence/methods , Macula Lutea/blood supply , Macula Lutea/diagnostic imaging , Macula Lutea/pathology , Retina/diagnostic imaging , Retina/pathology , Retina/physiopathology , Adolescent , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Retinal Vessels/physiopathologyABSTRACT
With the increase in the dependency on digital devices, the incidence of myopia, a precursor of various ocular diseases, has risen significantly. Because myopia and eyeball volume are related, myopia progression can be monitored through eyeball volume estimation. However, existing methods are limited because the eyeball shape is disregarded during estimation. We propose an automated eyeball volume estimation method from computed tomography images that incorporates prior knowledge of the actual eyeball shape. This study involves data preprocessing, image segmentation, and volume estimation steps, which include the truncated cone formula and integral equation. We obtained eyeball image masks using U-Net, HFCN, DeepLab v3 +, SegNet, and HardNet-MSEG. Data from 200 subjects were used for volume estimation, and manually extracted eyeball volumes were used for validation. U-Net outperformed among the segmentation models, and the proposed volume estimation method outperformed comparative methods on all evaluation metrics, with a correlation coefficient of 0.819, mean absolute error of 0.640, and mean squared error of 0.554. The proposed method surpasses existing methods, provides an accurate eyeball volume estimation for monitoring the progression of myopia, and could potentially aid in the diagnosis of ocular diseases. It could be extended to volume estimation of other ocular structures.
Subject(s)
Eye , Myopia , Neural Networks, Computer , Tomography, X-Ray Computed , Humans , Tomography, X-Ray Computed/methods , Eye/diagnostic imaging , Myopia/diagnostic imaging , Myopia/pathology , Female , Male , Adult , Image Processing, Computer-Assisted/methods , Middle Aged , Young AdultABSTRACT
BACKGROUND: Myopia is one of the most common eye diseases in children and adolescents worldwide, and scleral remodeling plays a role in myopia progression. However, the identity of the initiating factors and signaling pathways that induce myopia-associated scleral remodeling is still unclear. This study aimed to identify biomarkers of scleral remodeling to elucidate the pathogenesis of myopia. METHODS: The gene expression omnibus (GEO) and comparative toxicogenomics database (CTD) mining were used to identify the miRNA-mRNA regulatory network related to scleral remodeling in myopia. Real-time quantitative PCR (RT-qPCR), Western blot, immunofluorescence, H&E staining, Masson staining, and flow cytometry were used to detect the changes in the FOXO signaling pathway, fibrosis, apoptosis, cell cycle, and other related factors in scleral remodeling. RESULTS: miR-15b-5p/miR-379-3p can regulate the FOXO signaling pathway. Confirmatory studies confirmed that the axial length of the eye was significantly increased, the scleral thickness was thinner, the levels of miR-15b-5p, miR-379-3p, PTEN, p-PTEN, FOXO3a, cyclin-dependent kinase (CDK) inhibitor 1B (CDKN1B) were increased, and the levels of IGF1R were decreased in Len-induced myopia (LIM) group. CDK2, cyclin D1 (CCND1), and cell cycle block assessed by flow cytometry indicated G1/S cell cycle arrest in myopic sclera. The increase in BAX level and the decrease in BCL-2 level indicated enhanced apoptosis of the myopic sclera. In addition, we found that the levels of transforming growth factor-ß1 (TGF-ß1), collagen type 1 (COL-1), and α-smooth muscle actin (α-SMA) were decreased, suggesting scleral remodeling occurred in myopia. CONCLUSIONS: miR-15b-5p/miR-379-3p can regulate the scleral cell cycle and apoptosis through the IGF1R/PTEN/FOXO signaling pathway, thereby promoting scleral remodeling in myopia progression.
Subject(s)
Apoptosis , Cell Cycle , Forkhead Transcription Factors , MicroRNAs , Myopia , Sclera , Signal Transduction , Animals , Apoptosis/genetics , Base Sequence , Cell Cycle/genetics , Disease Models, Animal , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Myopia/genetics , Myopia/pathology , Myopia/metabolism , Sclera/pathology , Sclera/metabolismABSTRACT
High myopia can lead to pathologic myopia and visual impairment, whereas its causes are unclear. We retrospectively researched high myopia cases from patient records to investigate the association between axial elongation and myopic maculopathy. Sixty-four eyes were examined in patients who visited the department between July 2017 and June 2018, had an axial length of 26 mm or more, underwent fundus photography, and had their axial length measured twice or more. The average axial length was 28.29 ± 1.69 mm (mean ± standard deviation). The average age was 58.3 ± 14.4 years old. Myopic maculopathy was categorized as mild (grades 0 and 1) and severe (grades 2, 3, and 4). The severe group had longer axial lengths than the mild group (P < 0.05). Moreover, the severe group exhibited thinner choroidal thickness than the mild group (P < 0.05). When subjects were grouped by axial elongation over median value within a year, the elongation group showed thinner central choroidal thickness than the non-elongation group (142.1 ± 91.9 vs. 82.9 ± 69.8, P < 0.05). In conclusion, in patients with high myopia, the severity of maculopathy correlated with choroidal thickness and axial length. Thinner choroidal thickness was associated with axial elongation based on the baseline axial length.
Subject(s)
Axial Length, Eye , Choroid , Myopia , Humans , Female , Male , Middle Aged , Choroid/pathology , Choroid/diagnostic imaging , Aged , Retrospective Studies , Axial Length, Eye/pathology , Myopia/pathology , Myopia/complications , Adult , Severity of Illness Index , Tomography, Optical Coherence , Myopia, Degenerative/pathology , Visual Acuity , Retinal Diseases/pathology , Retinal Diseases/etiologyABSTRACT
Myopia represents a significant public health concern worldwide, particularly affecting the ocular health of children and adolescents. The escalating prevalence of myopia in recent years underscores its urgency as a health issue among this demographic. Research indicates a profound connection between the onset of myopia, inflammatory processes and fibrosis. Individuals with inflammatory conditions like allergic conjunctivitis, choroiditis, systemic lupus erythematosus, and diabetes exhibit a heightened susceptibility to myopia. Conversely, myopic patients are at an increased risk of developing ocular inflammatory disorders, notably idiopathic multifocal choroiditis. We postulate that the expression of inflammatory markers, including NF-κB, TGF-ß, IL-1ß, IL-6, IL-8, and TNF-α, may contribute to the chronic inflammatory state observed in myopia. This paper highlights a substantial correlation between myopia and inflammation, suggesting the potential efficacy of anti-inflammatory agents in managing inflammation and slowing myopia progression.
Subject(s)
Inflammation , Myopia , Child , Humans , Anti-Inflammatory Agents/therapeutic use , Cytokines/metabolism , Disease Progression , Inflammation/pathology , Myopia/epidemiology , Myopia/metabolism , Myopia/pathologyABSTRACT
Purpose: To compare changes in superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), and retinal thickness (RT) of the macular zone after repeated low-level red light (RLRL) and 0.01% atropine exposure in premyopic schoolchildren. Methods: Prospective randomized trial. Sixty-nine schoolchildren with cycloplegic refraction >-0.75 D and ≤0.50 D were randomly assigned to RLRL and 0.01% atropine groups. SRVD, DRVD, and RT were measured using swept-source optical coherence tomography at baseline and six months. The macular zone was divided into three concentric rings (fovea, parafovea, and perifovea) using the Early Treatment Diabetic Retinopathy Study. Results: After six months, the whole, parafoveal, and perifoveal SRVD significantly increased in the two groups (all P < 0.05). Multivariate regression analyses showed that none of these changes varied significantly between the two groups (all P > 0.05), whereas foveal SRVD remained stable in both groups (all P > 0.05). In the RLRL group, the whole and perifoveal DRVD increased significantly (all P < 0.05), whereas no statistical difference was observed in the foveal and parafoveal DRVD. DRVD remained stable in the 0.01% atropine group (all P > 0.05). No significant differences were observed in RT changes between the two groups (all P > 0.05). In comparison, there were no significant changes in SRVD, DRVD, or RT after six months in the placebo group in our previous study. Conclusions: SRVD increased similarly in the RLRL and 0.01% atropine groups, whereas DRVD increased only in the former group. There were no significant RT changes in either group after six months of treatment in premyopic schoolchildren. Translational Relevance: This research observed the effects of low-level red light and 0.01% atropine on retinal vasculature, offering valuable insights into myopia progression prevention.
Subject(s)
Atropine , Mydriatics , Retinal Vessels , Tomography, Optical Coherence , Humans , Atropine/administration & dosage , Atropine/pharmacology , Male , Female , Child , Prospective Studies , Retinal Vessels/drug effects , Retinal Vessels/diagnostic imaging , Mydriatics/administration & dosage , Mydriatics/pharmacology , Myopia/drug therapy , Myopia/pathology , Ophthalmic Solutions/administration & dosage , Ophthalmic Solutions/therapeutic use , Phototherapy/methods , Microvascular Density/drug effects , Red LightABSTRACT
The optic nerve head (ONH) is a complex structure wherein the axons of the retinal ganglion cells extrude from the eyeball through three openings: 1) the Bruch's membrane opening (BMO) in the retinal layer, 2) the anterior scleral canal opening in the anterior scleral layer, and 3) the lamina cribrosa (LC). Eyeball expansion during growth induces an offset among openings, since the expansion affects the inner retinal and outer scleral layers differently: the posterior polar retinal structure is preserved by the preferential growth in the equatorial region, whereas no such regional difference is observed in the scleral layer. The various modes and extents of eyeball expansion result in diverse directionality and amount of offset among openings, which causes diverse ONH morphology in adults, especially in myopia. In this review, we summarize the ONH changes that occur during myopic axial elongation. These changes were observed prospectively in our previous studies, wherein LC shift and subsequent offset from the BMO center could be predicted by tracing the central retinal vascular trunk position. This offset induces the formation of γ-zone parapapillary atrophy or externally oblique border tissue. As a presumptive site of glaucomatous damage, the LC/BMO offset may render the LC pores in the opposite direction more vulnerable. To support such speculation, we also summarize the relationship between LC/BMO offset and glaucomatous damage. Indeed, LC/BMO offset is not only the cause of diverse ONH morphology in adults, but is also, potentially, an important clinical marker for assessment of glaucoma.
Subject(s)
Bruch Membrane , Glaucoma , Optic Disk , Humans , Optic Disk/pathology , Bruch Membrane/pathology , Glaucoma/physiopathology , Glaucoma/pathology , Retinal Ganglion Cells/pathology , Intraocular Pressure/physiology , Eye/growth & development , Eye/pathology , Optic Nerve Diseases/physiopathology , Optic Nerve Diseases/pathology , Sclera/pathology , Myopia/pathology , Myopia/physiopathologyABSTRACT
Pou6f2 is a genetic connection between central corneal thickness (CCT) in the mouse and a risk factor for developing primary open-angle glaucoma. POU6F2 is also a risk factor for several conditions in humans, including glaucoma, myopia, and dyslexia. Recent findings demonstrate that POU6F2-positive retinal ganglion cells (RGCs) comprise a number of RGC subtypes in the mouse, some of which also co-stain for Cdh6 and Hoxd10. These POU6F2-positive RGCs appear to be novel of ON-OFF directionally selective ganglion cells (ooDSGCs) that do not co-stain with CART or SATB2 (typical ooDSGCs markers). These POU6F2-positive cells are sensitive to damage caused by elevated intraocular pressure. In the DBA/2J mouse glaucoma model, heavily-labeled POU6F2 RGCs decrease by 73% at 8 months of age compared to only 22% loss of total RGCs (labeled with RBPMS). Additionally, Pou6f2-/- mice suffer a significant loss of acuity and spatial contrast sensitivity along with an 11.4% loss of total RGCs. In the rhesus macaque retina, POU6F2 labels the large parasol ganglion cells that form the magnocellular (M) pathway. The association of POU6F2 with the M-pathway may reveal in part its role in human glaucoma, myopia, and dyslexia.
Subject(s)
Dyslexia , Glaucoma , Myopia , Retinal Ganglion Cells , Animals , Humans , Mice , Disease Models, Animal , Dyslexia/genetics , Dyslexia/metabolism , Dyslexia/pathology , Glaucoma/pathology , Glaucoma/metabolism , Glaucoma/genetics , Intraocular Pressure , Mice, Inbred DBA , Mice, Knockout , Myopia/pathology , Myopia/metabolism , Myopia/genetics , Retinal Ganglion Cells/pathology , Retinal Ganglion Cells/metabolism , Risk FactorsABSTRACT
The annual increase in myopia prevalence poses a significant economic and health challenge. Our study investigated the effect of calcitriol role in myopia by inducing the condition in guinea pigs through form deprivation for four weeks. Untargeted metabolomics methods were used to analyze the differences in metabolites in the vitreous body, and the expression of vitamin D receptor (VDR) in the retina was detected. Following form deprivation, the guinea pigs received intraperitoneal injections of calcitriol at different concentrations. We assessed myopia progression using diopter measurements and biometric analysis after four weeks. Results indicated that form deprivation led to a pronounced shift towards myopia, characterized by reduced choroidal and scleral thickness, disorganized collagen fibers, and decreased scleral collagen fiber diameter. Notably, a reduction in calcitriol expression in vitreous body, diminished vitamin D and calcitriol levels in the blood, and decreased VDR protein expression in retinal tissues were observed in myopic guinea pigs. Calcitriol administration effectively slowed myopia progression, preserved choroidal and scleral thickness, and prevented the reduction of scleral collagen fiber diameter. Our findings highlight a significant decrease in calcitriol and VDR expressions in myopic guinea pigs and demonstrate that exogenous calcitriol supplementation can halt myopia development, enhancing choroidal and scleral thickness and scleral collagen fiber diameter.
Subject(s)
Calcitriol , Myopia , Retina , Animals , Guinea Pigs , Myopia/metabolism , Myopia/drug therapy , Myopia/pathology , Calcitriol/pharmacology , Retina/metabolism , Retina/drug effects , Retina/pathology , Receptors, Calcitriol/metabolism , Receptors, Calcitriol/genetics , Male , Disease Models, Animal , Sclera/metabolism , Sclera/drug effects , Sclera/pathology , Choroid/metabolism , Choroid/drug effects , Choroid/pathology , Vitamin D/pharmacology , Vitamin D/administration & dosage , Axial Length, Eye , Vitreous Body/metabolism , Vitreous Body/drug effects , Disease Progression , Collagen/metabolismABSTRACT
Among the environmental factors contributing to myopia, the role of correlated color temperature (CCT) of ambient light emerges as a key element warranting in-depth investigation. The choroid, a highly vascularized and dynamic structure, often undergoes thinning during the progression of myopia, though the precise mechanism remains elusive. The retinal pigment epithelium (RPE), the outermost layer of the retina, plays a pivotal role in regulating the transport of ion and fluid between the subretinal space and the choroid. A hypothesis suggests that variations in choroidal thickness (ChT) may be modulated by transepithelial fluid movement across the RPE. Our experimental results demonstrate that high CCT illumination significantly compromised the integrity of tight junctions in the RPE and disrupted chloride ion transport. This functional impairment of the RPE may lead to a reduction in fluid transfer across the RPE, consequently resulting in choroidal thinning and potentially accelerating axial elongation. Our findings provide support for the crucial role of the RPE in regulating ChT. Furthermore, we emphasize the potential hazards posed by high CCT artificial illumination on the RPE, the choroid, and refractive development, underscoring the importance of developing eye-friendly artificial light sources to aid in the prevention and control of myopia.
Subject(s)
Chlorides , Choroid , Ion Transport , Retinal Pigment Epithelium , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/radiation effects , Retinal Pigment Epithelium/pathology , Choroid/metabolism , Choroid/radiation effects , Choroid/pathology , Animals , Ion Transport/radiation effects , Chlorides/metabolism , Lighting/methods , Temperature , Color , Tight Junctions/metabolism , Myopia/metabolism , Myopia/pathology , Myopia/etiologyABSTRACT
Purpose: This study aimed to evaluate the ocular characteristics associated with spontaneously high myopia in adult nonhuman primates (NHPs). Methods: A total of 537 eyes of 277 macaques with an average age of 18.53 ± 3.01 years (range = 5-26 years), raised in a controlled environment, were included. We measured ocular parameters, including spherical equivalent (SE), axial length (AXL), and intraocular pressure. The 45-degree fundus images centered on the macula and the disc assessed the fundus tessellation and parapapillary atrophy (PPA). Additionally, optical coherence tomography (OCT) was used to measure the thickness of the retinal nerve fiber layer (RNFL). Results: The mean SE was -1.58 ± 3.71 diopters (D). The mean AXL was 18.76 ± 0.86 mm. The prevalence rate of high myopia was 17.7%. As myopia aggravated, the AXL increased (r = -0.498, P < 0.001). Compared with non-high myopia, highly myopic eyes had a greater AXL (P < 0.001), less RNFL thickness (P = 0.004), a higher incidence of PPA (P < 0.001), and elevated grades of fundus tessellation (P < 0.001). The binary logistic regression was performed, which showed PPA (odds ratio [OR] = 4.924, 95% confidence interval [CI] = 2.375-10.207, P < 0.001) and higher grades of fundus tessellation (OR = 1.865, 95% CI = 1.474-2.361, P < 0.001) were independent risk characteristics for high myopia. Conclusions: In NHPs, a higher grade of fundus tessellation and PPA were significant biomarkers of high myopia. Translational Relevance: The study demonstrates adult NHPs raised in conditioned rooms have a similar prevalence and highly consistent fundus changes with human beings, which strengthens the foundation for utilizing macaques as an animal model in high myopic studies.
Subject(s)
Fundus Oculi , Tomography, Optical Coherence , Animals , Male , Female , Disease Models, Animal , Optic Disk/pathology , Optic Disk/diagnostic imaging , Optic Atrophy/pathology , Optic Atrophy/epidemiology , Intraocular Pressure/physiology , Myopia, Degenerative/pathology , Myopia, Degenerative/epidemiology , Nerve Fibers/pathology , Axial Length, Eye/pathology , Retinal Ganglion Cells/pathology , Myopia/pathology , Myopia/epidemiology , Myopia/veterinaryABSTRACT
BACKGROUND: Myopia is one of the eye diseases that can damage the vision of young people. This study aimed to explore the protective role of miR-92b-3p against DNA damage and apoptosis in retinal tissues of negative lens-induced myopic (LIM) guinea pigs by targeting BTG2. METHODS: Biometric measurements of ocular parameters, flash electroretinogram (FERG), and retinal thickness (RT) were performed after miR-92b-3p intravitreal injection in LIM guinea pigs. The apoptotic rate was detected by Annexin V-FITC/PI double staining, and the change in mitochondrial membrane potential was measured by JC-1 staining. Retinal apoptosis and expression of p53, BTG2, and CDK2 were explored by TdT-mediated dUTP-biotin nick labeling (TUNEL) and immunofluorescence staining assays, respectively. BTG2 and its upstream and downstream molecules at gene and protein levels in retinal tissues were measured by real-time quantitative PCR (qPCR) and Western blotting. RESULTS: Compared with normal controls (NC), the ocular axial length of LIM guinea pig significantly increased, whereas refraction decreased. Meanwhile, dMax-a and -b wave amplitudes of ERG declined, retinal thickness was decreased, the number of apoptotic cells and apoptotic rate in LIM eyes was exaggerated, and the mitochondrial membrane potential significantly decreased. In addition, results of qPCR and Western blot assays showed that the expression levels of p53, BTG2, CDK2, and BAX in LIM guinea pigs were higher than the levels of the NC group, whereas the BCL-2 expression level was decreased. By contrast, the miR-92b-3p intravitreal injection in LIM guinea pigs could significantly inhibit axial elongation, alleviate DNA damage and apoptosis, and thus protect guinea pigs against myopia. CONCLUSION: In conclusion, p53 and BTG2 were activated in the retinal tissue of myopic guinea pigs, and the activated BTG2 could elevate the expression of CDK2 and BAX, and attenuate the expression of BCL-2, which in turn promote apoptosis and eventually lead to retinal thinning and impaired visual function in myopic guinea pigs. The miR-92b-3p intravitreal injection can attenuate the elongation of ocular length and retinal thickness, and inhibit the CDK2, BAX, and p53 expression by targeting BTG2, thereby ameliorating DNA damage and apoptosis in LIM guinea pigs and protecting ocular tissues.
Subject(s)
Apoptosis , DNA Damage , MicroRNAs , Myopia , Retina , Animals , Guinea Pigs , MicroRNAs/genetics , MicroRNAs/metabolism , Retina/pathology , Retina/metabolism , Myopia/metabolism , Myopia/genetics , Myopia/pathology , Membrane Potential, Mitochondrial , Base Sequence , Immediate-Early Proteins/metabolism , Immediate-Early Proteins/genetics , Tumor Suppressor Proteins/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Protein p53/metabolism , Electroretinography , Disease Models, AnimalABSTRACT
INTRODUCTION: To investigate the levels of angiogenesis and inflammatory cytokines in individuals with myopic choroidal neovascularization (mCNV) and the changes in these factors following intravitreal anti-VEGF injection. METHODS: Aqueous humor samples were gathered from eyes with mCNV, those with single macular bleeding (SMB) without mCNV in highly myopic eyes, and those with age-related cataracts. Using a multiplex bead immunoassay, we analyzed 28 angiogenesis and inflammatory factors in the aqueous humor. Furthermore, clinical data were documented for correlation analysis. RESULTS: In this study, the levels of vascular endothelial growth factor A (VEGF-A), interleukin 8 (IL-8), and fibroblast growth factors 1 (FGF-1) were significantly elevated in mCNV compared to SMB eyes (p < 0.05). Their odds ratios for mCNV occurrence were 1.05, 3.45, and 2.64, respectively. Hepatocyte growth factor (HGF) and VEGF-C were notably higher in mCNV than in cataract patients (p < 0.05), and VEGF-C correlated to the degree of myopic atrophic maculopathy (p = 0.024). Axial length exhibited a negative correlation with VEGF-A and positive correlations with VEGF-C, HGF, and MCP-1 (p < 0.01). Following anti-VEGF treatment, a reduction in VEGF-A, endothelin-1, and FGF-2 was noted in mCNV patients (p < 0.05), but MCP-1 levels increased. CONCLUSION: Our findings highlight the predominant role of angiogenesis and inflammation factors in mCNV pathogenesis. VEGF-C's correlation with axial length and atrophy suggests its involvement in the process of myopic atrophic maculopathy.
Subject(s)
Choroidal Neovascularization , Myopia , Vascular Endothelial Growth Factor A , Humans , Choroidal Neovascularization/drug therapy , Choroidal Neovascularization/metabolism , Choroidal Neovascularization/pathology , Male , Female , Middle Aged , Aged , Vascular Endothelial Growth Factor A/metabolism , Myopia/drug therapy , Myopia/pathology , Myopia/metabolism , Myopia/complications , Intravitreal Injections , Inflammation/metabolism , Inflammation/pathology , Aqueous Humor/metabolism , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Cytokines/metabolism , Adult , AngiogenesisABSTRACT
To investigate the associations between corneal curvature (CC) and other anterior segment biometrics in young myopic adults. In this retrospective multi-center study, 7893 young myopic adults were included. CC and other anterior segment biometrics were measured by Scheimpflug imaging (Pentacam). CC was defined as SimK at central 3 mm area, and other anterior segment biometrics included white-to-white corneal diameter (WTW), central corneal thickness (CCT), corneal volume (CV) at 3 mm, 5 mm, and 7 mm area, anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), anterior corneal eccentricity (ACE) and asphericity (ACAP), posterior corneal eccentricity (PCE) and asphericity (PCAP), anterior chamber depth (ACD), and anterior chamber volume (ACV). Univariate regression analyses were used to assess the associations between CC and other anterior segment biometrics, and multivariate regression analyses were further performed to adjusted for age, gender and spherical equivalent. CC was higher in patients of female gender and higher myopia (all P < 0.05). Eyes in higher CC quartiles had lower WTW, thinner CCT, lower CV at 3 mm and 5 mm, lower ACD, and lower ACV (all P < 0.001), but had larger ACA, larger PCA, less PCE and less PCAP (all P < 0.001), compared to eyes in lower CC quartiles. The trends of CV at 7 mm, ACE and ACAP were inconsistent in different CC quartiles. After adjusting for age, gender and spherical equivalent with multivariate linear regression, CC was positively correlated to CV at 7 mm (ßs = 0.069), ACA (ßs = 0.194), PCA (ßs = 0.187), ACE (ßs = 0.072), PCAP (ßs = 0.087), and ACD (ßs = 0.027) (all P < 0.05), but was negatively correlated to WTW (ßs = - 0.432), CCT (ßs = - 0.087), CV-3 mm (ßs = - 0.066), ACAP (ßs = - 0.043), PCE (ßs = - 0.062), and ACV (ßs = - 0.188) (all P < 0.05). CC was associated with most of the other anterior segment biometrics in young myopic adults. These associations are important for better understanding of the interactions between different anterior segment structures in young myopic patients, and are also useful for the exploration of the pathogenesis of myopia.
Subject(s)
Astigmatism , Corneal Diseases , Myopia , Adult , Female , Humans , Anterior Chamber/diagnostic imaging , Anterior Chamber/pathology , Astigmatism/pathology , Biometry , Cornea/pathology , Corneal Diseases/pathology , Myopia/pathology , Retrospective StudiesABSTRACT
OBJECTIVES: To investigate the changes in the thickness of epithelium and stroma and their relationship with corneal curvature following the cessation of overnight orthokeratology for a period of 1 month. METHODS: This prospective study consecutively included 20 juveniles (20 right eyes) who had undergone overnight orthokeratology for a minimum of one year and were willing to discontinue the treatment. The study measured and compared epithelial and corneal curvature using optical coherence tomography and Medmont topographer at the first day of cessation and 1 month after cessation. In addition, changes in uncorrected visual acuity and refractive error before and after the cessation of the treatment were analyzed. RESULTS: The study found a significant increase in the thickness of the epithelium in the central 2-mm area after the cessation of the treatment (t = -4.807, P <0.001). Moreover, the stroma in the paracentral area (2-5 mm) and peripheral area (5-6 mm) showed a general thinning trend ( P =0.016, P =0.016). Regarding the correlation analysis, the change in central epithelial thickness (ΔCET) was significantly correlated with the change in paracentral corneal curvature (ΔPCCC) (r=0.610, P =0.007) and the change in peripheral corneal curvature (ΔPCC) (r=0.597, P =0.009). Similarly, the change in central stromal thickness (ΔCST) was significantly correlated with the change in central corneal curvature (ΔCCC) (r=0.500, P =0.035), ΔPCCC (r=0.700, P =0.001), and ΔPCC (r=0.635, P =0.005). CONCLUSIONS: The study found that the corneal remodeling induced by orthokeratology was reversible after the cessation of the treatment. Specifically, changes in the epithelium were found to be more prominent in the central area, while changes in the stroma were more pronounced in the paracentral and peripheral areas. In addition, the study established a significant correlation between central corneal remodeling and changes in curvature.
Subject(s)
Corneal Stroma , Corneal Topography , Epithelium, Corneal , Myopia , Orthokeratologic Procedures , Tomography, Optical Coherence , Visual Acuity , Humans , Orthokeratologic Procedures/methods , Prospective Studies , Corneal Stroma/pathology , Tomography, Optical Coherence/methods , Male , Epithelium, Corneal/pathology , Epithelium, Corneal/diagnostic imaging , Female , Visual Acuity/physiology , Myopia/therapy , Myopia/physiopathology , Myopia/pathology , Child , Adolescent , Refraction, Ocular/physiologyABSTRACT
The mechanisms underlying myopia remain not fully understood. We proposed to examine the function and underlying mechanisms of miR-204-5p in myopia development. The miR-204-5p expression level was assessed in the vitreous humor (VH) of a cohort consisting of 11 patients with high myopia (HM) and 16 control patients undergoing vitrectomy. Then the functional implications of miR-204-5p in ARPE-19 cells were assessed. Thioredoxin-interacting protein (TXNIP) was found as a possible target of miR-204-5p through mRNA sequencing, and its interaction with miR-204-5p was confirmed employing luciferase assay and western blotting. Furthermore, the miR-204-5p function in regulating oxidative stress was examined by measuring reactive oxygen species (ROS) accumulation. The results indicated a significant reduction of miR-204-5p in the VH of HM patients. Overexpression of miR-204-5p suppressed cell proliferation, migration, invasion, and apoptosis in ARPE-19 cells. The direct targeting of miR-204-5p on TXNIP has been confirmed, and its downregulation mediated the miR-204-5p impacts on ARPE-19 cells. Moreover, miR-204-5p overexpression significantly reduced ROS accumulation by targeting TXNIP. Our findings revealed the possible contribution of the miR-204-5p/TXNIP axis in myopia development by regulating oxidative stress, which may provide new targets to combat this prevalent and debilitating condition.
Subject(s)
Carrier Proteins , MicroRNAs , Myopia , Oxidative Stress , Reactive Oxygen Species , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Carrier Proteins/metabolism , Carrier Proteins/genetics , Myopia/genetics , Myopia/metabolism , Myopia/pathology , Reactive Oxygen Species/metabolism , Female , Cell Line , Cell Proliferation , Apoptosis/genetics , Male , Cell Movement/genetics , AdultABSTRACT
PURPOSE: To investigate the relationship between refraction and ocular axial length in albinos. PATIENTS AND METHODS: A cross-sectional, analytical study was carried out from June to November 2021 at the Central Hospital of Yaounde (Cameroon), which included consenting albino subjects aged over 15years. All subjects underwent visual acuity testing, axial length measurements and objective refraction under cycloplegia. RESULTS: We included 51 albino subjects. The mean age was 26.06±9.47years, and the sex ratio was 0.5. Type 2 oculocutaneous albinism (OCA2) was predominant, representing 82.4% of cases. The mean uncorrected visual acuity was 0.93±0.25 logMAR, and the most common ametropia was myopic astigmatism (52.9%). The mean axial length was 24.65±2.54mm with extremes of 21.54 and 30.33mm. Eyes with myopia and myopic astigmatism had significantly longer axial lengths than those with hyperopic and mixed astigmatism. A strong, significant negative correlation (r=-0.93; PË0.001) between the spherical component of the refraction and axial length was found. CONCLUSION: The spherical component of the refraction decreases significantly with increasing axial length in albinos.
Subject(s)
Axial Length, Eye , Refraction, Ocular , Humans , Male , Female , Refraction, Ocular/physiology , Adult , Cross-Sectional Studies , Young Adult , Adolescent , Axial Length, Eye/pathology , Middle Aged , Refractive Errors/epidemiology , Refractive Errors/diagnosis , Refractive Errors/physiopathology , Visual Acuity/physiology , Cameroon/epidemiology , Albinism/epidemiology , Albinism/complications , Myopia/diagnosis , Myopia/epidemiology , Myopia/physiopathology , Myopia/complications , Myopia/pathology , Correlation of DataABSTRACT
BACKGROUND AND OBJECTIVE: The prevalence of myopia and high myopia is increasing globally, underscoring the growing importance of diagnosing high myopia-related pathologies. While existing image segmentation models, such as U-Net, UNet++, ResU-Net, and TransUNet, have achieved significant success in medical image segmentation, they still face challenges when dealing with ultra-widefield (UWF) fundus images. This study introduces a novel automatic segmentation algorithm for the optic disc and peripapillary atrophy (PPA) based on UWF fundus images, aimed at assisting ophthalmologists in more accurately diagnosing high myopia-related diseases. METHODS: In this study, we developed a segmentation model leveraging a Transformer-based network structure, complemented by atrous convolution and selective boundary aggregation modules, to elevate the accuracy of segmenting the optic disc and PPA in UWF photography. The atrous convolution module adeptly manages multi-scale features, catering to the variances in target sizes and expanding the deep network's receptive field. Concurrently, the incorporation of the selective boundary aggregation module in the skip connections of the model significantly improves the differentiation of boundary information between segmentation targets. Moreover, the comparison of our proposed algorithm with classical segmentation models like U-Net, UNet++, ResU-Net, and TransUNet highlights its considerable advantages in processing UWF photographs. RESULTS: The experimental results show that, compared to the other four models, our algorithm demonstrates substantial improvements in segmenting the optic disc and PPA in UWF photographs. In PPA segmentation, our algorithm improves by 0.8% in Dice, 1.8% in sensitivity, and 1.3% in intersection over union (IOU). In optic disc segmentation, our algorithm improves by 0.3% in Dice, 0.6% in precision, and 0.4% in IOU. CONCLUSION: Our proposed method improves the segmentation accuracy of PPA and optic disks based on UWF photographs, which is valuable for diagnosing high myopia-related diseases in ophthalmology clinics.