A highly efficient murine model of experimental myopia.
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ABSTRACT:
SUBMITTER: Jiang X
PROVIDER: S-EPMC5794929 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeSeveral recent studies have suggested that experimental myopia can be induced in mice. However, it is not clear what role the photopic visual input plays in this process and whether mouse myopia is similar to human myopia. The purpose of this study was to carry out an in vivo high-resolution analysis of changes in ocular components and refractive state of the eye upon induction of experimental myopia in mice.MethodsA high-resolution small animal MRI system and a high-resolution automated eccentric infrared photorefractor were used to analyze changes of the refractive state and ocular components in C57BL/6J mice associated with experimental myopia induced by diffusers and -25 D lenses under photopic conditions.ResultsThe authors found that both diffusers and -25 D lenses induce myopia in C57BL/6J mice under photopic conditions (continuous light, 200 +/- 15 lux). The extent of myopic shift induced by -25 D lenses was greater than the shift induced by diffusers (-15.2 +/- 0.7 D, lenses; -12.0 +/- 1.4 D, diffusers). Myopia in mice is attributed to an increase in size of the postequatorial segment of the eye. Experimental myopia in mice can be induced only during the susceptible period in postnatal development, which ends around postnatal day 67.ConclusionsBoth diffusers and spectacle lenses induce myopia in mice under photopic conditions, during the susceptible period in postnatal development. Myopia in mice is associated with elongation of the vitreous chamber of the eye, as in humans and nonhuman primates.
| S-EPMC2829371 | biostudies-literature
Project description:Periodontal disease (PD) is a common dental disease associated with the interaction between dysbiotic oral microbiota and host immunity. It is a prevalent disease, resulting in loss of gingival tissue, periodontal ligament, cementum and alveolar bone. PD is a major form of tooth loss in the adult population. Experimental animal models have enabled the study of PD pathogenesis and are used to test new therapeutic approaches for treating the disease. The ligature-induced periodontitis model has several advantages as compared with other models, including rapid disease induction, predictable bone loss and the capacity to study periodontal tissue and alveolar bone regeneration because the model is established within the periodontal apparatus. Although mice are the most convenient and versatile animal models used in research, ligature-induced periodontitis has been more frequently used in large animals. This is mostly due to the technical challenges involved in consistently placing ligatures around murine teeth. To reduce the technical challenge associated with the traditional ligature model, we previously developed a simplified method to easily install a bacterially retentive ligature between two molars for inducing periodontitis. In this protocol, we provide detailed instructions for placement of the ligature and demonstrate how the model can be used to evaluate gingival tissue inflammation and alveolar bone loss over a period of 18 d after ligature placement. This model can also be used on germ-free mice to investigate the role of human oral bacteria in periodontitis in vivo. In conclusion, this protocol enables the mechanistic study of the pathogenesis of periodontitis in vivo.
| S-EPMC6773250 | biostudies-literature
Project description:Juvenile primates develop myopia when their visual experience is degraded by lid fusion. In response to the abnormal visual input, retinal neural networks cause an excessive growth of the postequatorial segment of the eye, but the mechanism underlying this axial elongation is unknown. By combining analysis of gene expression, injection of the thymidine analog 5-bromo-2'-deoxyuridine and immunocytochemistry, we show that the retinal periphery in both juvenile rhesus macaques and green monkeys harbors a population of mitotically active neuroprogenitor cells that proliferate when the visual experience is altered by lid fusion. Furthermore, the number of dividing cells is highly correlated with the axial elongation of the eye and the resulting myopic refractive error. Thus, the retina undergoes active growth during the postnatal development of the primate eye. This growth is modulated by the visual input and accelerates considerably when the eye develops axial myopia. cDNA subtractions, construction of cDNA libraries and differential screening were performed as previously described (Tkatchenko et al, 2000). Two subtractions were carried out resulting in two cDNA libraries. One library was enriched in clones potentially up-regulated in the retina of the closed eye and the other was enriched in cDNAs potentially down-regulated. One thousand clones from each library were analyzed, and 535 differentially-expressed cDNAs were amplified by PCR and spotted onto glass slides coated with poly-L-lysine (five duplicates for each cDNA). The slides were then processed, hybridized with Cy3- and Cy5-labeled complex cDNA probes and washed in 0.2xSSC as described at http://cmgm.stanford.edu/pbrown/protocols/. Two hybridizations with color swap were carried for each monkey. After hybridization, slides were scanned using a GenePix 4000B microarray scanner (Axon Instruments, Union City, CA). The images were acquired and processed using the GenePix Pro 5.1 software package (Axon Instruments). The data obtained were normalized against GAPDH expression level and mean values (the reported values) and P-values (probability associated with a Student's t-test) were calculated for duplicate experiments (n = 10) with color swap using Microsoft Excel. Genes were defined as differentially regulated if P< 0.05. Cluster analysis was performed using the Genesis software package (provided by Alexander Sturn, Graz University of Technology, Austria).
2010-07-01 | E-GEOD-3300 | biostudies-arrayexpress
Project description:To identify tissues and molecules involved in refractive myopic shift and axial length elongation in a murine lens-induced myopia model, we performed a comprehensive analysis of microRNA (miRNA) expression. Three weeks after negative 30 diopter lens fixation on three-week-old C57BL/6J mice, total RNA was extracted from individual ocular components including cornea, iris, lens, retina, retinal pigment epithelium (RPE)/choroid, and sclera tissue. The miRNA expression analysis was pooled from three samples and carried out using Agilent Mouse miRNA Microarray (8 × 60 K) miRBase21.0. The expression ratio was calculated, and differentially expressed miRNAs were extracted, using GeneSpring GX 14.5. Myopic induction showed a significant myopic refractive change, axial elongation, and choroidal thinning. Through the comprehensive miRNA analysis, several upregulated miRNAs (56 in cornea tissue, 13 in iris tissue, 6 in lens tissue, 0 in retina tissue, 29 in RPE/choroid tissue, and 30 in sclera tissue) and downregulated miRNAs (7 in cornea tissue, 28 in iris tissue, 17 in lens tissue, 9 in retina tissue, 7 in RPE/choroid tissue, and 40 in sclera tissue) were observed. Overlapping expression changes in miRNAs were also found in different ocular components. Some of this miRNA dysregulation may be functionally involved in refractive myopia shift and axial length elongation.
| S-EPMC6695704 | biostudies-literature
Project description:To identify to identify target tissues and molecules involved with refractive myopic shift and axial length elongation in a murine lens-induced myopia model, we performed comprehensive analysis by microRNA array. Negative 30diptor (-30D) lens was fixed on right eye (-30D) of C57BL/6J mice (3weeks old, N=3) for 3 weeks, the refraction and the axial length were measured using a refractometer and a SD-OCT system in all eyes. Eye balls were enucleated and separated to cornea, iris, lens, retina, choroid and sclera. Total RNA was extracted from individual ocular components. MicroRNA expression analysis was carried out using Agilent Mouse miRNA Microarray (8×60K) miRBase21.0 (Agilent). Expression ratio calculation and miRNA varying expression were extracted by GeneSpring GX 14.5 (Agilent). After 3weeks of lens fixing, a refractive change and an axial length elongation change were observed (Normal vs -30D: 0.95 ± 1.85D vs -18.42 ± 3.98D, 0.155 mm ± 0.015mm vs 0.273 ± 0.009 mm), respectively. MiRNA expression changes that induced only by -30D lens fixing was confirmed in each part of the eyeball. By expression ratio calculation and miRNA varying expression analysis, upregulated miRNA (56 in cornea, 13 in iris, 6 in lens, 0 in retina, 29 in choroid and 30 in sclera) and downregulated miRNA (7 in cornea, 28 in iris, 17 in lens, 9 in retina, 7 in choroid and 40 in sclera) were observed. Overlapping miRNAs were also found while each eye tissues. In this study, miRNA varying expression were observed in each ocular part of the murine lens-induced myopia model. These miRNAs dysregulation may be functionally involved with the refractive myopia shift and the axial length elongation.
2019-05-29 | GSE131831 | GEO
Project description:Juvenile primates develop myopia when their visual experience is degraded by lid fusion. In response to the abnormal visual input, retinal neural networks cause an excessive growth of the postequatorial segment of the eye, but the mechanism underlying this axial elongation is unknown. By combining analysis of gene expression, injection of the thymidine analog 5-bromo-2'-deoxyuridine and immunocytochemistry, we show that the retinal periphery in both juvenile rhesus macaques and green monkeys harbors a population of mitotically active neuroprogenitor cells that proliferate when the visual experience is altered by lid fusion. Furthermore, the number of dividing cells is highly correlated with the axial elongation of the eye and the resulting myopic refractive error. Thus, the retina undergoes active growth during the postnatal development of the primate eye. This growth is modulated by the visual input and accelerates considerably when the eye develops axial myopia. Keywords: disease state analysis
2006-02-27 | GSE3300 | GEO
Project description:Multiphoton absorption may find many technological applications, such as enhancing the conversion efficiency of solar cells by the utilization of sub-band-energy photons, below-bandgap photodetection through the simultaneous absorption of several infrared photons for photocurrent generation, or light frequency upconversion for high-resolution, 3D imaging. To enhance multiphoton absorption in semiconducting materials, one of the strategies is to explore low-dimensional excitons. Here, a quantum perturbation theory on a giant enhancement in three-photon absorption (3PA) arising from 2D excitons in multilayered crystals of organic-inorganic hybrid perovskites is presented. The maximal 3PA coefficient is predicted to be in the range of 2-7 cm3 GW-2 at 1100 nm, the largest values reported so far for any 2D and bulk semiconductors at room temperature. Excellent agreement between theory and the experimental findings unambiguously demonstrates a pivotal role in the enhancement of 3PA played by 2D excitons. The theory predicts that the resonant 3PA coefficient should be enhanced further by at least two orders of magnitude with very low temperature. The findings are essential for understanding giant 3PA arising from 2D excitons in layered hybrid perovskites and may open new pathways for highly efficient conversion from infrared light energy to either electrical energy or higher-frequency light emission/lasing.
| S-EPMC6382301 | biostudies-literature
Project description:Increased global incidence of myopia necessitates establishment of therapeutic approaches against its progression. To explore agents which may control myopia, we screened 207 types of natural compounds and chemical reagents based on an activity of a myopia suppressive factor, early growth response protein 1 (Egr-1) in vitro. Among the candidates, crocetin showed the highest and dose-dependent activation of Egr-1. For in vivo analysis, experimental myopia was induced in 3-week-old C57BL/6 J mice with -30 diopter (D) lenses for 3 weeks. Animals were fed with normal or mixed chow containing 0.003% (n = 19) and 0.03% (n = 7) of crocetin during myopia induction. Refraction and axial length were measured at 3-week-old and the 6-week-old with an infrared photorefractor and a SD-OCT system. Compared to controls (n = 14), crocetin administration showed a significant smaller change of refractive errors (-13.62 ± 8.14 vs +0.82 ± 5.81 D for 0.003%, p < 0.01, -2.00 ± 4.52 D for 0.03%, p < 0.01) and axial elongation (0.27 ± 0.03 vs 0.22 ± 0.04 mm for 0.003%, p < 0.01, 0.23 ± 0.05 mm for 0.03%, p < 0.05). These results suggest that a dietary factor crocetin may have a preventive effect against myopia progression.
| S-EPMC6343000 | biostudies-literature
Project description:Our understanding of the mechanisms that regulate hematopoietic stem/progenitor cells (HSPCs) has been advanced by the ability to genetically manipulate mice; however, germline modification is time consuming and expensive. Here, we describe fast, efficient, and cost-effective methods to directly modify the genomes of mouse and human HSPCs using the CRISPR/Cas9 system. Using plasmid and virus-free delivery of guide RNAs alone into Cas9-expressing HSPCs or Cas9-guide RNA ribonucleoprotein (RNP) complexes into wild-type cells, we have achieved extremely efficient gene disruption in primary HSPCs from mouse (>60%) and human (?75%). These techniques enabled rapid evaluation of the functional effects of gene loss of Eed, Suz12, and DNMT3A. We also achieved homology-directed repair in primary human HSPCs (>20%). These methods will significantly expand applications for CRISPR/Cas9 technologies for studying normal and malignant hematopoiesis.
| S-EPMC5087995 | biostudies-literature
Project description:The generation efficiencies of mutation-induced mice when using engineered zinc-finger nucleases (ZFNs) have been generally 10 to 20% of obtained pups in previous studies. The discovery of high-affinity DNA-binding modules can contribute to the generation of various kinds of novel artificial chromatin-targeting tools, such as zinc-finger acetyltransferases, zinc-finger histone kinases and so on, as well as improvement of reported zinc-finger recombinases and zinc-finger methyltransferases. Here, we report a novel ZFN pair that has a highly efficient mutation-induction ability in murine zygotes. The ZFN pair induced mutations in all obtained mice in the target locus, exon 17 of aminopeptidase Q gene, and almost all of the pups had biallelic mutations. This high efficiency was also shown in the plasmid DNA transfected in a cultured human cell line. The induced mutations were inherited normally in the next generation. The zinc-finger modules of this ZFN pair are expected to contribute to the development of novel ZF-attached chromatin-targeting tools.
| S-EPMC4685226 | biostudies-literature