Pigment Epithelium-Derived Factor Reduces Apoptosis and Pro-Inflammatory Cytokine Gene Expression in a Murine Model of Focal Retinal Degeneration

Wang, Yujuan; Subramanian, Preeti; Shen, Defen; Tuo, Jingsheng; Becerra, S. Patricia; Chan, Chi‐Chao

doi:10.1042/an20130028

Cited by 49 publications

(42 citation statements)

References 58 publications

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“…The mice were anesthetized and injected subconjunctivally (at the 2-3 o'clock position) with 1, 2, 5, or 25 mg/mL bevacizumab (Avastin; Roche Pharma, Basel, Switzerland; 5 lL per eye) one, two, or four times (injection every 2 days). For the recovery experiment, mice were injected simultaneously with bevacizumab (5 mg/ mL) and recombinant mouse pigment epithelium-derived factor (PEDF; R&D, San Diego, CA, USA; 15 ng/lL, 5 lL per eye), nerve growth factor (NGF; R&D; 20 ng/lL, 5 lL per eye) or ciliary neurotrophic factor (CNTF; R&D; 10 ng/lL, 5 lL per eye), in accordance with previous reports [32][33][34] and our preliminary experiments. Normal saline (0.9% NaCl) was injected as vehicle control.…”

Section: Methods and Materials Subconjunctival Bevacizumab Injection mentioning

confidence: 89%

Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice

Dong

Zhang

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Dong M, Di G, Zhang X, Zhou Q, Shi W. Subconjunctival bevacizumab injection impairs corneal innervations and epithelial wound healing in mice. Invest Ophthalmol Vis Sci. 2017;58:146958: -147758: . DOI: 10.1167 PURPOSE. To investigate the effects of subconjunctival bevacizumab injection on the corneal nerve, sensitivity, and epithelial wound healing in mice.METHODS. Adult C57BL/6 mice were treated with subconjunctival injection of 1, 2, 5, or 25 mg/mL bevacizumab. The corneal nerve was observed with whole-mount anti-b3-tubulin fluorescence staining. Corneal sensitivity was measured with a Cochet-Bonnet esthesiometer. The protein levels of pigment epithelium-derived factor (PEDF), nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), and ciliary neurotrophic factor (CNTF) were measured by ELISA. The corneal epithelial wound-healing rate was evaluated by fluorescein staining. The recovery of impaired mouse corneal innervations and epithelial wound-healing rate following bevacizumab injection was evaluated with the co-injection of PEDF, NGF, or CNTF.RESULTS. Subconjunctival bevacizumab injection caused apparent corneal nerve degeneration, attenuated corneal sensitivity, and delayed corneal epithelial wound healing and nerve regeneration in normal mice, which was more significant with increased concentration and times of the bevacizumab injection. However, the corneal nerve and sensitivity gradually improved and recovered in mice with a single injection of 1 to 5 mg/mL bevacizumab. Moreover, the bevacizumab injection significantly decreased the corneal PEDF, NGF, and CNTF content, whereas exogenous PEDF, NGF, or CNTF supplement attenuated impairment of the corneal nerve, sensitivity, and epithelial wound healing after subconjunctival bevacizumab injection.CONCLUSIONS. Subconjunctival bevacizumab injection impairs corneal innervations, epithelial wound healing, and nerve regeneration in normal mice, which may be caused by the reduction of neurotrophic factor content in the cornea.

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Section: Methods and Materials Subconjunctival Bevacizumab Injection mentioning

confidence: 89%

Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice

Dong

Zhang

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Our results indicate that SalB blocks the CMS-induced increases in apoptosis in both the hippocampus and cortex and prevents the decrease of hippocampal volume and cell density. Interestingly, activated microglia were recruited into the regions of apoptosis and a significant correlation between apoptosis and microglial activation was observed both in the hippocampus and cortex, thereby indicating that CMS-induced apoptosis is associated with a microglia-mediated pro-inflammatory response [49] . Moreover, we observed that apoptotic cells were phagocytized by activated microglia, which suggests that microglia plays a dual role in the phagocytosis of apoptotic cells and the regulation of neuroinflammation.…”

Section: Discussionmentioning

confidence: 97%

Salvianolic acid B ameliorates depressive-like behaviors in chronic mild stress-treated mice: involvement of the neuroinflammatory pathway

Zhang

Feng

et al. 2016

Acta Pharmacol Sin

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Aim: Major depressive disorder (MDD) is a debilitating mental disorder associated with dysfunction of the neurotransmitterneuroendocrine system and neuroinflammatory responses. Salvianolic acid B (SalB) has shown a variety of pharmacological activities, including anti-inflammatory, antioxidant and neuroprotective effects. In this study, we examined whether SalB produced antidepressantlike actions in a chronic mild stress (CMS) mouse model, and explored the mechanisms underlying the antidepressant-like actions of SalB. Methods: Mice were subjected to a CMS paradigm for 6 weeks. In the last 3 weeks the mice were daily administered SalB (20 mg·kg -1 ·d -1 , ip) or a positive control drug imipramine (20 mg·kg -1 ·d -1 , ip). The depressant-like behaviors were evaluated using the sucrose preference test, the forced swimming test (FST), and the tail suspension test (TST). The gene expression of cytokines in the hippocampus and cortex was analyzed with RT-PCR. Plasma corticosterone (CORT) and cerebral cytokines levels were assayed with an ELISA kit. Neural apoptosis and microglial activation in brain tissues were detected using immunofluorescence staining. Results: Administration of SalB or imipramine reversed the reduced sucrose preference ratio of CMS-treated mice, and significantly decreased their immobility time in the FST and TST. Administration of SalB significantly decreased the expression of pro-inflammatory cytokines IL-1β and TNF-α, and markedly increased the expression of anti-inflammatory cytokines IL-10 and TGF-β in the hippocampus and cortex of CMS-treated mice, and normalized their elevated plasma CORT levels, whereas administration of imipramine did not significantly affect the imbalance between pro-and anti-inflammatory cytokines in the hippocampus and cortex of CMS-treated mice. Finally, administration of SalB significantly decreased CMS-induced apoptosis and microglia activation in the hippocampus and cortex, whereas administration of imipramine had no significant effect on CMS-induced apoptosis and microglia activation in the hippocampus and cortex. Conclusion: SalB exerts potent antidepressant-like effects in CMS-induced mouse model of depression, which is associated with the inhibiting microglia-related apoptosis in the hippocampus and the cortex.

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“…The research on cellular and molecular mechanisms underlying learning impairment in MHE is currently underway. Proinflammatory molecules (such as TNF-α) can interact with each other to evoke apoptosis and tissue damage, resulting in retinal degeneration [47].…”

Section: Discussionmentioning

confidence: 99%

Dopamine Burden Triggers Neurodegeneration via Production and Release of TNF-α from Astrocytes in Minimal Hepatic Encephalopathy

Ding

Wang

et al. 2015

Mol Neurobiol

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Dopamine (DA)-induced learning and memory impairment is well documented in minimal hepatic encephalopathy (MHE), but the contribution of DA to neurodegeneration and the involved underlying mechanisms are not fully understood. In this study, the effect of DA on neuronal apoptosis was initially detected. The results showed that MHE/DA (10 μg)-treated rats displayed neuronal apoptosis. However, we found that DA (10 μM) treatment did not induce evident apoptosis in primary cultured neurons (PCNs) but did produce TNF-α in primary cultured astrocytes (PCAs). Furthermore, co-cultures between PCAs and PCNs exposed to DA exhibited increased astrocytic TNF-α levels and neuronal apoptosis compared with co-cultures exposed to the vehicle, indicating the attribution of the neuronal apoptosis to astrocytic TNF-α. We also demonstrated that DA enhanced TNF-α production from astrocytes by activation of the TLR4/MyD88/NF-κB pathway, and secreted astrocytic TNF-α-potentiated neuronal apoptosis through inactivation of the PI3K/Akt/mTOR pathway. Overall, the findings from this study suggest that DA stimulates substantial production and secretion of astrocytic TNF-α, consequently and indirectly triggering progressive neurodegeneration, resulting in cognitive decline and memory loss in MHE.

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Pigment Epithelium-Derived Factor Reduces Apoptosis and Pro-Inflammatory Cytokine Gene Expression in a Murine Model of Focal Retinal Degeneration

Cited by 49 publications

References 58 publications

Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice

Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice

Salvianolic acid B ameliorates depressive-like behaviors in chronic mild stress-treated mice: involvement of the neuroinflammatory pathway

Dopamine Burden Triggers Neurodegeneration via Production and Release of TNF-α from Astrocytes in Minimal Hepatic Encephalopathy

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