TMP Prevents Retinal Neovascularization and Imparts Neuroprotection in an Oxygen-Induced Retinopathy Model

Liang, Xiaoling; Zhou, Huanjiao Jenny; Ding, Yuan; Li, Jie; Yang, Cheng; Luo, Yan; Li, Shiqing; Sun, Gang; Liao, Xulong; Wang, Min

doi:10.1167/iovs.11-9315

Cited by 46 publications

(53 citation statements)

References 65 publications

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“…ocular diseases, including corneal neovascularization and glaucoma. [21][22][23][24] In the present study, our results indicate that TMP exhibits an inhibitory effect on the proliferation in profibrotic cytokine-treated HTFs. Moreover, in 10% FBS, HTFs treated with TMP were less viable and expressed less PCNA, but were not apoptotic even at a high concentration (400 lM), indicating that the limiting effects of TMP were unlikely to be due to toxicity.…”

Section: Discussionsupporting

confidence: 64%

“…19,20 Accumulating evidence suggests that TMP may have therapeutic potential as a complementary therapy for various ocular diseases, including vascular retinopathy, corneal neovascularization, optic neuropathy, and glaucoma. 16,[21][22][23] In particular, our latest investigation implicated TMP in attenuation of TGF-b-induced pathologic changes in trabecular meshwork cells, showing that it inhibits cytoskeleton remodeling and ECM accumulation through the SDF/CXCR4 axis. 24 Prompted by these previous reports, we sought to characterize the bioactivity of TMP and its underlying mechanism.…”

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confidence: 99%

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Tetramethylpyrazine Attenuates Transdifferentiation of TGF-β2–Treated Human Tenon's Fibroblasts

Cai

Yang

Chen

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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Citation: Cai X, Yang Y, Chen P, et al. Tetramethylpyrazine attenuates transdifferentiation of TGF-b2-treated human Tenon's fibroblasts. Invest Ophthalmol Vis Sci. 2016;57:4740-4748. DOI:10.1167/iovs.16-19529 PURPOSE. To investigate the pharmacologic effect of tetramethylpyrazine (TMP) on human Tenon's fibroblasts (HTFs), the cells implicated in scarring after filtration surgery. METHODS.Transforming growth factor-b2 (TGF-b2) was used to stimulate a fibrotic phenotype in primary HTFs, and the influence of TMP on the fibrotic phenotype was assessed. Cell proliferation and cell cycle regulation were profiled. Immunofluorescence staining tracked proliferating cell nuclear antigen (PCNA) expression. Transwell assays monitored cell migration. Flow cytometry measured TMP toxicity. In addition, in TGF-b2-treated HTFs, Western blot and immunofluorescence were employed to assess the expression of a-smooth muscle actin (a-SMA). The TMP-mediated activity on cytoskeletal arrangements and extracellular matrix (ECM) accumulation in HTFs was evaluated using actin polymerization and Western blot assays. Moreover, TGF-b-dependent activation of Smad3 and p38 was examined by Western blot analysis. RESULTS.In TGF-b2-treated HTFs, TMP reduced proliferation and migration but did not induce apoptosis. Moreover, TMP attenuated expression of a-SMA and suppressed stress fiber formation stimulated by profibrotic cytokine; it also counteracted TGF-b2-induced cytoskeletal rearrangements, morphologic changes, and ECM accumulation. Smad3 and p38 mitogenactivated protein kinase (MAPK) signaling were downstream of the TMP-sensitive effect.CONCLUSIONS. Tetramethylpyrazine counteracts TGF-b2-mediated myofibroblast transdifferentiation and attenuates ECM component deposition and cell proliferation in HTFs, implicating TMP as a potential antifibrosis agent in glaucoma filtration surgery.

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Section: Discussionsupporting

confidence: 64%

mentioning

confidence: 99%

Tetramethylpyrazine Attenuates Transdifferentiation of TGF-β2–Treated Human Tenon's Fibroblasts

Cai

Yang

Chen

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…19,20 Mouse Model of Oxygen-Induced Retinopathy Oxygen-induced retinopathy was induced in mice using the protocol of Smith and colleagues 6,7 as we recently described. 31 On postnatal day 7 (P7), pups with their dams were placed in a 75% oxygen (hyperoxia, H) chamber for 5 days and returned to room air (relative hypoxia) from P12 to P17. Age-matched mice raised under normoxia (N) served as controls.…”

Section: Animal Protocolmentioning

confidence: 99%

“…Fifteen sections on each side of the optic nerve, at least 40 lm apart, were used to assess NV in a doubleblinded manner via counting of EC nuclei anterior to the internal limiting membrane (on the vitreal side) as previously described. 6,7,31 Eyes from six mice of each genotype group were analyzed, and the number of endothelial nuclei per section was averaged for each eye.…”

Section: Quantification Of Neovascular Nucleimentioning

confidence: 99%

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Functional Analyses of TNFR2 in Physiological and Pathological Retina Angiogenesis

Wan

Zhou

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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Wnt inhibitory 1 ameliorates neovascularization and attenuates photoreceptor injury in an oxygen‐induced retinopathy mouse model

Tan

Chen

et al. 2022

BioFactors

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Retinal neovascularization (RNV) associated diseases typically exhibit pathological neovascularization and neurodegeneration. Wnt inhibitor factor 1 (WIF1) is a secreted Wnt antagonist that regulates angiogenesis. However, the significance of WIF1 in RNV associated disease has not been explicitly tested. In our study, we found that the WIF1 expressions were strongly downregulated in the vitreous of proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP). Similarly, retinal WIF1 expression was significantly downregulated in OIR mice, relative to normal mice at P17. After injection of WIF1 overexpression lentivirus into the vitreous of OIR mice, overexpressing WIF1 in OIR mice vitreous strongly reduced avascular areas and neovascular tufts, increased vessel branches, raised a‐, b‐waves and oscillatory potentials amplitudes on ERG, increased retinal thickness and the number of synapses in retina, normalized the Golgi, mitochondria, and outer segments of photoreceptors. Furthermore, overexpression WIF1 suppressed expressions of β‐catenin, vascular endothelial growth factor (VEGF), p‐AKT and p‐ERK, reduced retinal reactive oxygen species (ROS) and 4‐HNE levels, improved autophagic flux, and mitigated apoptosis. In summary, WIF1 plays a key role in alleviating angiogenesis and in improving visual function in OIR mice by suppressing the Wnt/β‐catenin‐VEGF signaling pathway and ROS levels. WIF1 is an excellent candidate for targeted therapy against RNV associated diseases.

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TMP Prevents Retinal Neovascularization and Imparts Neuroprotection in an Oxygen-Induced Retinopathy Model

Abstract: TMP improved neurovascular recovery by preventing NV and protecting retinal astroglia cells and neurons from ischemia-induced cell death partially due to its downregulation of HIF-1α and VEGF mRNA expression.

Cited by 46 publications

References 65 publications

Tetramethylpyrazine Attenuates Transdifferentiation of TGF-β2–Treated Human Tenon's Fibroblasts

Tetramethylpyrazine Attenuates Transdifferentiation of TGF-β2–Treated Human Tenon's Fibroblasts

Functional Analyses of TNFR2 in Physiological and Pathological Retina Angiogenesis

Wnt inhibitory 1 ameliorates neovascularization and attenuates photoreceptor injury in an oxygen‐induced retinopathy mouse model

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