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

Ouyang, Xinli; Han, Yangyang; Xie, Yongfang; Wu, Yide; Guo, Shaojia; Cheng, Min; Wang, Guohui

doi:10.1016/j.biopha.2019.109294

Cited by 23 publications

(15 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Past research suggests that scleral collagen synthesis, degradation, and crosslinking play important roles during emmetropization, and this balance is altered during myopia. 27 , 28 We hypothesized that collagen fibers in the sclera of mfrp mutants may be altered and contribute to their improper emmetropization. To test this, we imaged collagen fibers in the central posterior region of the scleral stroma by TEM ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Recent work suggests that collagen bundle size is dynamically regulated during emmetropization, and these alterations in size can change their mechanical properties. 27 Recently, alterations in scleral collagen dynamics have been partially attributed to an increased presence of scleral macrophages in a visual form-deprived mouse model of myopia. 28 These investigators reported that macrophages appeared to be recruited to the sclera of form-deprived myopic mice by increased scleral expression of C-C motif chemokine ligand-2.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ablation of mpeg⁺ Macrophages Exacerbates mfrp-Related Hyperopia

Brandt

Collery

Besharse

et al. 2021

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose Proper refractive development of the eye, termed emmetropization, is critical for focused vision and is impacted by both genetic determinants and several visual environment factors. Improper emmetropization caused by genetic variants can lead to congenital hyperopia, which is characterized by small eyes and relatively short ocular axial length. To date, variants in only four genes have been firmly associated with human hyperopia, one of which is MFRP . Zebrafish mfrp mutants also have hyperopia and, similar to reports in mice, exhibit increased macrophage recruitment to the retina. The goal of this research was to examine the effects of macrophage ablation on emmetropization and mfrp- related hyperopia. Methods We utilized a chemically inducible, cell-specific ablation system to deplete macrophages in both wild-type and mfrp mutant zebrafish. Spectral-domain optical coherence tomography was then used to measure components of the eye and determine relative refractive state. Histology, immunohistochemistry, and transmission electron microscopy were used to further study the eyes. Results Although macrophage ablation does not cause significant changes to the relative refractive state of wild-type zebrafish, macrophage ablation in mfrp mutants significantly exacerbates their hyperopic phenotype, resulting in a relative refractive error 1.3 times higher than that of non-ablated mfrp siblings. Conclusions Genetic inactivation of mfrp leads to hyperopia, as well as abnormal accumulation of macrophages in the retina. Ablation of the mpeg1-positive macrophage population exacerbates the hyperopia, suggesting that macrophages may be recruited in an effort help preserve emmetropization and ameliorate hyperopia.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ablation of mpeg⁺ Macrophages Exacerbates mfrp-Related Hyperopia

Brandt

Collery

Besharse

et al. 2021

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…Significantly, we found alteration to scleral collagen fibril size in mfrp mutants, as well as the modulation of collagen fibril size by macrophage ablation. Recent work suggests that collagen bundle size is dynamically regulated during emmetropization, and these alterations in size can change their mechanical properties 23 . Recently a change in scleral collagen dynamics has been partially attributed to an increased presence of scleral macrophages in a visual form-deprived mouse model of myopia 24 .…”

Section: Discussionmentioning

confidence: 99%

“…Past research suggests that scleral collagen synthesis, degradation, and crosslinking play important roles during emmetropization, and this balance is altered during myopia 23,24 . We hypothesized that collagen fibers in the sclera of mfrp mutants may be altered and contribute to their improper emmetropization.…”

Section: Macrophage Ablation Alters Collagen Bundle Sizementioning

confidence: 99%

Ablation ofmpeg+ macrophages exacerbatesmfrp-related hyperopia

Besharse

et al. 2021

Preprint

View full text Add to dashboard Cite

PURPOSE: Proper refractive development of the eye, termed emmetropization, is critical for focused vision and impacted by both genetic determinants and several visual environment factors. Improper emmetropization caused by genetic variants can lead to congenital hyperopia, which is characterized by small eyes and relatively short ocular axial length. To date variants in only four genes have been firmly associated with human hyperopia, one of which is MFRP. Zebrafish mfrp mutants also have hyperopia and similar to reports in mice, exhibit increased macrophage recruitment to the retina. The goal of this research was to examine the effects of macrophage ablation on emmetropization and mfrp-related hyperopia. METHODS: We utilized a chemically inducible, cell-specific ablation system to deplete macrophages in both wild-type and mfrp mutant zebrafish. Spectral-domain optical coherence tomography (SD-OCT) was used to measure components of the eye and determine relative refractive state. Histology, immunohistochemistry, and transmission electron microscopy was used to further study the eyes. RESULTS: While macrophage ablation does not cause significant changes to the relative refractive state of wild-type zebrafish, macrophage ablation in mfrp mutants significantly exacerbates their hyperopic phenotype. CONCLUSIONS: Genetic inactivation of mfrp leads to hyperopia as well as abnormal accumulation of macrophages in the retina. Ablation of the mpeg1-positive macrophage population exacerbates the hyperopia, suggesting that macrophages are recruited in an effort help preserve emmetropization and ameliorate hyperopia.

show abstract

“…The mechanism of myopia is not completely understood, but AL elongation and scleral remodeling are considered important processes during myopia development [7]. During this development, scleral collagen decomposition is greater than synthesis [27]. The increase in collagen degradation is regulated by MMPs and TIMPs [11,15].…”

Section: Discussionmentioning

confidence: 99%

Association between MMP/TIMP Levels in the Aqueous Humor and Plasma with Axial Lengths in Myopia Patients

Hsiao

Zhou

2020

BioMed Research International

View full text Add to dashboard Cite

Purpose. The present study investigated the profiles of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) of the aqueous humor (AH) and plasma (PL) in myopia patients, to determine whether there was an association between these levels with their axial length (AL) and to investigate if MMPs/TIMPs were regulated locally or systemically. Methods. A cross-sectional study was conducted. Thirty-nine patients (78 eyes) diagnosed with high myopia were recruited. The AL was measured using IOL Master. And the patients were divided into three groups based on their AL, Group A (AL≤26 mm), Group B (26<AL≤28 mm), and Group C (AL>28 mm). The AH in both eyes and blood samples were collected before the patients underwent implantable collamer lens surgery. In all, 78 samples of the AH and 39 samples of the PL were analyzed using MILLIPLEX map assays, followed by statistical analyses of the results. Results. There were 8 patients (16 eyes) in Group A, 22 patients (44 eyes) in Group B, and 9 patients (18 eyes) in Group C. MMP-1 (p=0.014, Β=0.118), MMP-2 (p≤0.001, Β=0.278), MMP-9 (p≤0.001, Β=0.019), and TIMP-1 (p=0.014, Β=0.062) in the AH were positively associated with the AL. MMP-1 (p=0.004, Β=0.001) and TIMP-1 (p=0.030, Β=1.171) concentrations in the PL increased linearly with longer ALs. No concentration-dependent relationship was found between MMP-2 in the PL and AL. Conclusions. There was a consistent relationship between MMP-2 in the AH and AL. AL was not consistently or substantially affected by MMP-2 in the PL, indicating myopia formation was possibly a localized process. Associations among MMP-1, MMP-9, and TIMP-1 in the AH and AL were also observed.

show abstract

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

Cited by 23 publications

References 16 publications

Ablation of mpeg⁺ Macrophages Exacerbates mfrp-Related Hyperopia

Ablation of mpeg⁺ Macrophages Exacerbates mfrp-Related Hyperopia

Ablation ofmpeg+ macrophages exacerbatesmfrp-related hyperopia

Association between MMP/TIMP Levels in the Aqueous Humor and Plasma with Axial Lengths in Myopia Patients

Contact Info

Product

Resources

About

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

Cited by 23 publications

References 16 publications

Ablation of mpeg+ Macrophages Exacerbates mfrp-Related Hyperopia

Ablation of mpeg+ Macrophages Exacerbates mfrp-Related Hyperopia

Ablation ofmpeg+ macrophages exacerbatesmfrp-related hyperopia

Association between MMP/TIMP Levels in the Aqueous Humor and Plasma with Axial Lengths in Myopia Patients

Contact Info

Product

Resources

About

Ablation of mpeg⁺ Macrophages Exacerbates mfrp-Related Hyperopia

Ablation of mpeg⁺ Macrophages Exacerbates mfrp-Related Hyperopia