Genipin inhibits the scleral expression of miR-29 and MMP2 and promotes COL1A1 expression in myopic eyes of guinea pigs

Wang, Min; Yang, Zhikuan; Liu, Hong; Li, Ruiqin; Liu, Yu; Zhong, Wenjun

doi:10.1007/s00417-020-04634-7

Cited by 19 publications

(11 citation statements)

References 21 publications

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“…The Col1a1 and Mmp2 genes have been reported to encode the extracellular matrix component collagen and are engaged in extracellular matrix remodeling in the sclera [31,32]. In addition, the proteins encoded by Col1a1 and Mmp2 are involved in angiogenesis and the myopia pathway (among other activities) in mice and guinea pigs [33][34][35][36]. Here, we found that the expression levels of these two genes were upregulated in the retina after the intravitreal injection of brimonidine.…”

Section: Discussionmentioning

confidence: 68%

Intravitreal brimonidine inhibits form-deprivation myopia in guinea pigs

Yang

et al. 2021

Eye and Vis

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Background The use of ocular hypotensive drugs has been reported to attenuate myopia progression. This study explores whether brimonidine can slow myopia progression in the guinea pig form-deprivation (FD) model. Methods Three-week-old pigmented male guinea pigs (Cavia porcellus) underwent monocular FD and were treated with 3 different methods of brimonidine administration (eye drops, subconjunctival or intravitreal injections). Four different concentrations of brimonidine were tested for intravitreal injection (2 μg/μL, 4 μg/μL, 20 μg/μL, 40 μg/μL). All treatments continued for a period of 21 days. Tonometry, retinoscopy, and A-scan ultrasonography were used to monitor intraocular pressure (IOP), refractive error and axial length (AL), respectively. On day 21, guinea pigs were sacrificed for RNA sequencing (RNA-seq) to screen for associated transcriptomic changes. Results The myopia model was successfully established in FD animals (control eye vs. FD eye, respectively: refraction at day 20, 0.97 ± 0.18 D vs. − 0.13 ± 0.38 D, F = 6.921, P = 0.02; AL difference between day 0 and day 21, 0.29 ± 0.04 mm vs. 0.45 ± 0.03 mm, F = 11.655, P = 0.004). Among the 3 different brimonidine administration methods, intravitreal injection was the most effective in slowing myopia progression, and 4 μg/μL was the most effective among the four different concentrations of brimonidine intravitreal injection tested. The AL and the refraction of the brimonidine intravitreal injection group was significantly shorter or more hyperopic than those of other 2 groups. Four μg/μL produced the smallest difference in AL and spherical equivalent difference values. FD treatment significantly increased the IOP. IOP was significantly lower at 1 day after intravitreal injections which was the lowest in FD eye of intravitreal injection of brimonidine. At day 21, gene expression analyses using RNA-seq showed upregulation of Col1a1 and Mmp2 expression levels by intravitreal brimonidine. Conclusions Among the 3 different administration methods, intravitreal injection of brimonidine was the most effective in slowing myopia progression in the FD guinea pig model. Intravitreal brimonidine at 4 μg/μL significantly reduced the development of FD myopia in guinea pigs. Expression levels of the Col1a1 and Mmp2 genes were significantly increased in the retinal tissues of the FD-Inj-Br group.

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Section: Discussionmentioning

confidence: 68%

Intravitreal brimonidine inhibits form-deprivation myopia in guinea pigs

Yang

et al. 2021

Eye and Vis

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“…Western blot analysis was performed as previously described (Wang et al 2020b). After treatment, the cells or exosomes were lysed and total protein was extracted using the radioimmunoprecipitation assay lysis buffer (Beyotime).…”

Section: Western Blotmentioning

confidence: 99%

Exosomal miR-223 derived from natural killer cells inhibits hepatic stellate cell activation by suppressing autophagy

Wang

Quan

2020

Mol Med

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Background: Activation of hepatic stellate cells (HSCs) is a prominent driver of liver fibrosis. We previously demonstrated that exosomes derived from natural killer (NK) cells (NK-Exo) attenuated TGF-β1-induced HSC activation. Herein, this study was designed to investigate the mechanism underlying the action of NK-Exo. Methods: NK-Exo was isolated from NK-92MI cells and then administered into TGF-β1-treated LX-2 (human HSC line) cells. MiR-223 expression in NK-Exo was downregulated by transfecting NK-92MI cells with miR-223 inhibitor followed by exosome isolation. The HSC activation was evaluated by determining cell proliferation using CCK-8 assay and measuring the protein levels of α-SMA and CoL1A1 using western blot in LX-2 cells. The expression of miR-223 was detected by qRT-PCR. The interaction between miR-223 and ATG7 was analyzed by a dual-luciferase activity assay. The autophagy was evaluated by measuring the autophagy-related proteins using western blot. Results: miR-223 was highly expressed in NK-Exo and inhibition of miR-223 expression in NK-Exo abrogated the inhibitory effect of NK-Exo on TGF-β-induced HSC activation. ATG7 was confirmed as a direct target of miR-223. Furthermore, treatment with the autophagy activator rapamycin and ATG7 overexpression in LX-2 cells abolished the HSC activation-suppressive effect of NK-Exo. Conclusion: NK-Exo attenuated TGF-β-induced HSC activation by transferring miR-223 that inhibited autophagy via targeting ATG7.

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“… 19 , 20 As a recognized ECM regulator, miR‐29a has been found to affect the expression of collagen I through Wnt/β‐catenin signalling pathway. 21 Other miRNAs, such as miR‐184, miR‐29a and miR‐let‐7i, have also been associated with myopia. However, the regulatory mechanism of miRNAs in myopia has not been explicitly described in previous studies.…”

Section: Introductionmentioning

confidence: 99%