Advances in biomedical study of the myopia-related signaling pathways and mechanisms.

Myopia has become one of the most critical health problems in the world with the increasing time spent indoors and increasing close work. Pathological myopia may have multiple complications, such as myopic macular degeneration, retinal detachment, cataracts, open-angle glaucoma, and severe cases that can cause blindness. Mounting evidence suggests that the cause of myopia can be attributed to the complex interaction of environmental exposure and genetic susceptibility. An increasing number of researchers have focused on the genetic pathogenesis of myopia in recent years. Scleral remodeling and excessive axial elongating induced retina thinning and even retinal detachment are myopia's most important pathological manifestations. The related signaling pathways are indispensable in myopia occurrence and development, such as dopamine, nitric oxide, TGF-ß, HIF-1α, etc. We review the current major and recent progress of biomedicine on myopia-related signaling pathways and mechanisms.

Whole transcriptome analysis on blue light-induced eye damage.

AIM: To analyze abnormal gene expressions of mice eyes exposed to blue light using RNA-seq and analyze the related signaling pathways. METHODS: Kunming mice were divided into an experimental group that was exposed to blue light and a control group that was exposed to natural light. After 14d, the mice were euthanized and their eyeballs were collected. Whole transcriptome analysis was attempted to analyze the gene expression of the eyeballs using RNA-seq to reconstruct genetic networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to reveal the related signaling pathways. RESULTS: The 737 differentially expressed genes were identified, including 430 up and 307 down regulated genes, by calculating the gene FPKM in each sample and conducting differential gene analysis. GO and KEGG pathway enrichment analysis showed that blue light damage may associated with the visual perception, sensory perception of light stimulus, phototransduction, and JAK-STAT signaling pathways. Differential lncRNA, circRNA and miRNA analysis showed that blue light exposure affected pathways for retinal cone cell development and phototransduction, among others. CONCLUSION: Exposure to blue light can cause a certain degree of abnormal gene expression and modulate signaling pathways in the eye.

Mechanisms of blue light-induced eye hazard and protective measures: a review.

The risk of blue light exposure to human health has attracted increased research attention. Blue light, with relatively high energy, can cause irreversible photochemical damage to eye tissue. Excessive exposure of the eye to blue light tends to cause a series of alterations, such as oxidative stress, mitochondrial apoptosis, inflammatory apoptosis, mitochondrial apoptosis and DNA damage, resulting in the development of dry eye disease, glaucoma, and keratitis. Accordingly, physical protection, chemical and pharmaceutical protective measures, gene therapy, and other methods are widely used in the clinical treatment of blue light hazard. We reviewed the studies on possible blue light-induced signaling pathways and mechanisms in the eye and summarized the therapeutic approaches to addressing blue light hazard.

Mechanical strain affects collagen metabolism-related gene expression in scleral fibroblasts.

We previously demonstrated that collagen metabolism affects scleral mechanical properties and scleral remodeling. Scleral remodeling changes the mechanical strain on sclera and scleral fibroblasts. We postulated that mechanical strain changes affect collagen metabolism in scleral fibroblasts. To understand the differences in collagen metabolism in scleral fibroblasts related to mechanical strain changes, scleral fibroblasts were isolated and cultured under different mechanical strains using the FX-4000 system or were treated with the TGF-ß1 and TGFBR1 inhibitor LY364947. The collagen metabolism-related gene expression levels were detected. The results showed that the appropriate (lower) mechanical strain improved collagen synthesis and reduced collagen decomposition. In contrast, higher mechanical strain reduced collagen synthesis and enhanced collagen decomposition, especially a sustained higher strain. Furthermore, the effect of a transitory higher strain was recoverable, and collagen metabolism in scleral fibroblasts was regulated by TGF-ß1. These results suggested that mechanical strain mediates TGF-ß1 expression to regulate collagen metabolism in scleral fibroblasts, thereby affect scleral tissue remodeling.

Co-culture and Mechanical Stimulation on Mesenchymal Stem Cells and Chondrocytes for Cartilage Tissue Engineering.

Defects in articular cartilage injury and chronic osteoarthritis are very widespread and common, and the ability of injured cartilage to repair itself is limited. Stem cell-based cartilage tissue engineering provides a promising therapeutic option for articular cartilage damage. However, the application of the technique is limited by the number, source, proliferation, and differentiation of stem cells. The co-culture of mesenchymal stem cells and chondrocytes is available for cartilage tissue engineering, and mechanical stimulation is an important factor that should not be ignored. A combination of these two approaches, i.e., co-culture of mesenchymal stem cells and chondrocytes under mechanical stimulation, can provide sufficient quantity and quality of cells for cartilage tissue engineering, and when combined with scaffold materials and cytokines, this approach ultimately achieves the purpose of cartilage repair and reconstruction. In this review, we focus on the effects of co-culture and mechanical stimulation on mesenchymal stem cells and chondrocytes for articular cartilage tissue engineering. An in-depth understanding of the impact of co-culture and mechanical stimulation of mesenchymal stem cells and chondrocytes can facilitate the development of additional strategies for articular cartilage tissue engineering.

The collagen metabolism affects the scleral mechanical properties in the different processes of scleral remodeling.

PURPOSE: To increase the understanding of collagen metabolism as related to scleral remodeling in the process of emmetropization and myopization. METHODS: An eyelid suture that lasted 60 days was performed on one-month-old rabbits to establish an experimental monocular visual deprivation myopia model and the axial length was recorded. HE staining and transmission electron microscope were used to observe the scleral structure. The Instron 5544 was used to measure scleral elastic modulus after measuring the scleral thickness. The content of scleral tissue collagen was determined by detecting the hydroxyproline quantity and the collagen I α1, MMP-2, and TIMP-2 mRNA expression were detected by RT-PCR Kit. RESULTS: During regular emmetropization, the scleral collagen synthesis was higher than decomposition and the diameter of collagen fibrils increased, and then the sclera thickened and mechanical properties improved. During myopization, the scleral collagen decomposition was higher than synthesis and the diameter of collagen fibrils was smaller, and then the sclera thinner and mechanical properties lower, which resulted in a difference in scleral tissue strain. CONCLUSION: The results suggested that there were different scleral remodeling process between the emmetropization and myopization, and the collagen metabolism affected the scleral mechanical properties and scleral remodeling and then affected the scleral growth, axial elongation, and even myopization.

Mechanical stimulation promotes the proliferation and the cartilage phenotype of mesenchymal stem cells and chondrocytes co-cultured in vitro.

Mesenchymal stem cells and chondrocytes are an important source of the cells for cartilage tissue engineering. Therefore, the culture and expansion methods of these cells need to be improved to overcome the aging of chondrocytes and induced chondrogenic differentiation of mesenchymal stem cells. The aim of this study was to expand the cells for cartilage tissue engineering by combining the advantages of growing cells in co-culture and under a mechanically-stimulated environment. Rabbit chondrocytes and co-cultured cells (bone mesenchymal stem cells and chondrocytes) were subjected to cyclic sinusoidal dynamic tensile mechanical stimulationusing the FX-4000 tension system. Chondrocyte proliferation was assayed by flow cytometry and CFSE labeling. The cell cartilage phenotype was determined by detecting GAG, collagen II and TGF-ß1 protein expression by ELISA and the Col2α1, TGF-ß1 and Sox9 gene expression by RT-PCR. The results show that the co-culture improved both the proliferation ability of chondrocytes and the cartilage phenotype of co-cultured cells. A proper cyclic sinusoidal dynamic tensile mechanical stimulation improved the proliferation ability and cartilage phenotype of chondrocytes and co-cultured cells. These results suggest that the co-culture of mesenchymal stem cells with chondrocytes and proper mechanical stimulation may be an appropriate way to rapidly expand the cells that have an improved cartilage phenotype for cartilage tissue engineering.