scholarly journals Glabridin Attenuates the Retinal Degeneration Induced by Sodium Iodate In Vitro and In Vivo

2020 ◽  
Vol 11 ◽  
Author(s):  
Kaung Htet Aung ◽  
Hua Liu ◽  
Zongwen Ke ◽  
Shuang Jiang ◽  
Jianhua Huang
Keyword(s):  
Retinal Degeneration ◽  
Sodium Iodate

scholarly journals Inhibition of DUSP6 Activates Autophagy and Rescues the Retinal Pigment Epithelium in Sodium Iodate-Induced Retinal Degeneration Models In Vivo and In Vitro

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 159
Author(s):  
Hao-Yu Tsai ◽  
Henkie Isahwan Ahmad Mulyadi Lai ◽  
Zhang-Yuan Chen ◽  
Tai-Chi Lin ◽  
Winnie Khor ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Retinal Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Autophagic Flux ◽  
Erk Pathway ◽  
Sodium Iodate ◽  
Autophagy Flux

Autophagy plays a protective role in the retinal pigment epithelium (RPE) by eliminating damaged organelles in response to reactive oxygen species (ROS). Dual-specificity protein phosphatase 6 (DUSP6), which belongs to the DUSP subfamily, works as a negative-feedback regulator of the extracellular signal-regulated kinase (ERK) pathway. However, the complex interplay between DUSP6 and autophagy induced by ROS in RPE is yet to be investigated. To investigate the relationship between DUSP6 and autophagy, we exposed the ARPE-19 cell line and C57BL/6N mice to sodium iodate (NaIO3) as an oxidative stress inducer. Our data showed that the inhibition of DUSP6 activity promotes autophagy flux through the ERK pathway via the upregulation of immunoblotting expression in ARPE-19 cells. Live imaging showed a significant increase in autophagic flux activities, which suggested the restoration autophagy after treatment with the DUSP6 inhibitor. Furthermore, the mouse RPE layer exhibited an irregular structure and abnormal deposits following NaIO3 injection. The retina layer was recovered after being treated with DUSP6 inhibitor; this suggests that DUSP6 inhibitor can rescue retinal damage by restoring the mouse retina’s autophagy flux. This study suggests that the upregulation of DUSP6 can cause autophagy flux malfunctions in the RPE. The DUSP6 inhibitor can restore autophagy induction, which may serve as a potential therapeutic approach for retinal degeneration disease.

scholarly journals The effects of intravitreal sodium iodate injection on retinal degeneration following vitrectomy in rabbits

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
So Min Ahn ◽  
Jungryul Ahn ◽  
Seongkwang Cha ◽  
Cheolmin Yun ◽  
Tae Kwann Park ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Intravitreal Injection ◽  
Dose Dependence ◽  
Sodium Iodate ◽  
New Zealand White Rabbits ◽  
Retinal Atrophy ◽  
Response Change ◽  
The Right ◽  
Sd Oct

Abstract We sought to develop and characterize outer retinal degeneration induced by intravitreal injection of sodium iodate (SI) after vitrectomy in rabbits. To determine the effective dose of SI, the right eyes of 19 male New Zealand white rabbits received an intravitreal injection of SI or sham. Based on the dose-dependence results, 0.4 mg of SI in 0.05 mL of total volume was injected into the right eyes of 10 rabbits at two weeks after vitrectomy. In the dose-dependence study, localized retinal atrophy was observed with 0.3- and 0.4-mg SI injections without vitrectomy. Severe and diffuse retinal atrophy was identified by spectral-domain optical coherence tomography (SD-OCT) at one month after a 0.5-mg SI injection following vitrectomy. In the second experiment, 0.4 mg of SI in 0.05 mL was injected, and the severity of outer retinal degeneration was graded as one of two types according to electroretinography (ERG) response change. There was no response on ERG in complete retinal degeneration, 30% of all 10 rabbits. Intravitreal injection of 0.4 mg of SI into vitrectomized rabbit eyes induces diffuse outer retinal degeneration, and the degree of retinal degeneration can be evaluated through in vivo ophthalmic examination.

scholarly journals Indole-3-carbinol regulates microglia homeostasis and protects the retina from degeneration

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Amir Saeed Khan ◽  
Thomas Langmann
Keyword(s):  
Retinal Degeneration ◽  
Therapeutic Option ◽  
Retinal Cell ◽  
Subretinal Space ◽  
Western Blots ◽  
Protein Levels ◽  
Qrt Pcr ◽  
Anti Oxidant

Abstract Background Retinal degenerative diseases significantly contribute to visual impairment and blindness. Microglia reactivity is a hallmark of neurodegenerative diseases including retinal cell death and immunomodulation emerges as a therapeutic option. Indole-3-carbinol (I3C) is a natural ligand of aryl hydrocarbon receptor (AhR), with potent immunomodulatory properties. Here, we hypothesized that I3C may inhibit microglia reactivity and exert neuroprotective effects in the light-damaged murine retina mimicking important immunological aspects of retinal degeneration. Methods BV-2 microglia were treated in vitro with I3C followed by lipopolysaccharide (LPS) stimulation to analyze pro-inflammatory and anti-oxidant responses by quantitative real-time PCR (qRT-PCR) and Western blots. Nitric oxide (NO) secretion, caspase 3/7 levels, phagocytosis rates, migration, and morphology were analyzed in control and AhR knockdown cells. I3C or vehicle was systemically applied to light-treated BALB/cJ mice as an experimental model of retinal degeneration. Pro-inflammatory and anti-oxidant responses in the retina were examined by qRT-PCR, ELISA, and Western blots. Immunohistochemical staining of retinal flat mounts and cryosections were performed. The retinal thickness and structure were evaluated by in vivo imaging using spectral domain-optical coherence tomography (SD-OCT). Results The in vitro data showed that I3C potently diminished LPS-induced pro-inflammatory gene expression of I-NOS, IL-1ß, NLRP3, IL-6, and CCL2 and induced anti-oxidants gene levels of NQO1, HMOX1, and CAT1 in BV-2 cells. I3C also reduced LPS-induced NO secretion, phagocytosis, and migration as important functional microglia parameters. siRNA-mediated knockdown of AhR partially prevented the previously observed gene regulatory events. The in vivo experiments revealed that I3C treatment diminished light-damage induced I-NOS, IL-1ß, NLRP3, IL-6, and CCL2 transcripts and also reduced CCL2, I-NOS, IL-1ß, p-NFkBp65 protein levels in mice. Moreover, I3C increased anti-oxidant NQO1 and HMOX1 protein levels in light-exposed retinas. Finally, I3C therapy prevented the accumulation of amoeboid microglia in the subretinal space and protected from retinal degeneration. Conclusions The AhR ligand I3C potently counter-acts microgliosis and light-induced retinal damage, highlighting a potential treatment concept for retinal degeneration.

scholarly journals The Phosphatidylinositol Transfer Protein Domain of Drosophila Retinal Degeneration B Protein Is Essential for Photoreceptor Cell Survival and Recovery from Light Stimulation

1997 ◽  
Vol 139 (2) ◽  
pp. 351-363 ◽  
Author(s):  
Scott C. Milligan ◽  
James G. Alb ◽  
Raya B. Elagina ◽  
Vytas A. Bankaitis ◽  
David R. Hyde
Keyword(s):  
Retinal Degeneration ◽  
Light Response ◽  
Protein Domain ◽  
Inherited Disease ◽  
Light Stimulation ◽  
Transfer Protein ◽  
Phosphatidylinositol Transfer Protein ◽  
Phosphatidylinositol Transfer

The Drosophila retinal degeneration B (rdgB) gene encodes an integral membrane protein involved in phototransduction and prevention of retinal degeneration. RdgB represents a nonclassical phosphatidylinositol transfer protein (PITP) as all other known PITPs are soluble polypeptides. Our data demonstrate roles for RdgB in proper termination of the phototransduction light response and dark recovery of the photoreceptor cells. Expression of RdgB's PITP domain as a soluble protein (RdgB-PITP) in rdgB2 mutant flies is sufficient to completely restore the wild-type electrophysiological light response and prevent the degeneration. However, introduction of the T59E mutation, which does not affect RdgB-PITP's phosphatidylinositol (PI) and phosphatidycholine (PC) transfer in vitro, into the soluble (RdgB-PITP-T59E) or full-length (RdgB-T59E) proteins eliminated rescue of retinal degeneration in rdgB2 flies, while the light response was partially maintained. Substitution of the rat brain PITPα, a classical PI transfer protein, for RdgB's PITP domain (PITPα or PITPα-RdgB chimeric protein) neither restored the light response nor maintained retinal integrity when expressed in rdgB2 flies. Therefore, the complete repertoire of essential RdgB functions resides in RdgB's PITP domain, but other PITPs possessing PI and/or PC transfer activity in vitro cannot supplant RdgB function in vivo. Expression of either RdgB-T59E or PITPα-RdgB in rdgB+ flies produced a dominant retinal degeneration phenotype. Whereas RdgB-T59E functioned in a dominant manner to significantly reduce steady-state levels of rhodopsin, PITPα-RdgB was defective in the ability to recover from prolonged light stimulation and caused photoreceptor degeneration through an unknown mechanism. This in vivo analysis of PITP function in a metazoan system provides further insights into the links between PITP dysfunction and an inherited disease in a higher eukaryote.

scholarly journals Ferulic acid attenuates microglia-mediated neuroinflammation in retinal degeneration

2020 ◽  
Author(s):  
Xiaowei Sun ◽  
Peng Sun ◽  
Limei Liu ◽  
Pengfei Jiang ◽  
YUANBIN LI
Keyword(s):  
Ferulic Acid ◽  
Retinal Degeneration ◽  
Microglial Activation ◽  
Inflammatory Factors ◽  
Immunomodulatory Activity ◽  
Retinal Structure ◽  
The Impact ◽  
Optimal Protection

Abstract Background: Retinal degeneration is often accompanied by microglia-mediated neuroinflammation. Ferulic acid (FA), an active ingredient of traditional Chinese medicines (TCMs), has been reported to have anti-inflammatory effects. This study explores the impact of FA on microglia-mediated neuroinflammation and associated retinal degeneration in rd10 mice. Methods: Rd10 mice received different concentrations of FA every day from postnatal day (P)4 to P24. On P25, the visual function of the mice was evaluated by electroretinogram, and retinae were collected for further investigation. Microglial activation and the expression of relevant cytokines in the retina were evaluated by qPCR, western blotting and immunofluorescence staining. Retinal structure was assessed by haematoxylin and eosin (HE) staining.Results: Supplementation with 50 mg/kg FA provided optimal protection against retinal degeneration, with treated mice exhibiting more photoreceptor nuclei as well as greater wave amplitude amplification on electroretinogram than untreated mice. FA suppressed microglial activation both in vivo and in vitro, and inhibited the expression of pro-inflammatory factors Tnfα, IL1β, and Ccl2 in the retinae of rd10 mice. Furthermore, FA suppressed the activation of STAT1 and subsequently inhibited IRF8 expression, potentially highlighting a role for these pathways in FA-mediated immunomodulatory activity. Conclusions: Attenuation of neuroinflammation by FA may be beneficial for retarding retinal degeneration.

scholarly journals Ferulic acid attenuates microglia-mediated neuroinflammation in retinal degeneration

2020 ◽  
Author(s):  
Xiaowei Sun ◽  
Peng Sun ◽  
Limei Liu ◽  
Pengfei Jiang ◽  
YUANBIN LI
Keyword(s):  
Ferulic Acid ◽  
Retinal Degeneration ◽  
Microglia Activation ◽  
Immunofluorescent Staining ◽  
Inflammatory Factors ◽  
Immunomodulatory Activity ◽  
Ccl2 Expression ◽  
The Impact

Abstract Background: To use a rd10 mouse model as a means of exploring the impact of Ferulic acid(FA) on microglia-mediated neuroinflammation as well as associated retinal degeneration. Methods: Rd10 mice received different concentrations of FA treatment every day from postnatal day (P)4 to P24. At P25, mice visual function were detected by electroretinogram, then retinae were collected for further investigation. Retinal microglia activation state and relevant cytokines were evaluated by qPCR, Western blot and immunofluorescent staining. The retinal structure was assessed by HE Staining. Results:50mg/Kg FA supplement exhibited optimal protection against retinal degeneration, with treated mice exhibiting more photoreceptor nuclei as well as significant wave amplitude amplification in electroretinograms. FA suppressed microglia activation both in vivo and in vitro, inhibited pro-inflammatory factors Tnfα, IL1β, Ccl2 expression in rd10 retinae. Furthermore, FA suppressed the activation of STAT1 and subsequently IRF8 expression, potentially highlighting a role for these pathways in FA-mediated immunomodulatory activity. Conclusions: Attenuating neuroinflammation by FA may be beneficial to retard retinal degeneration.

scholarly journals Ferulic acid attenuates microglia-mediated neuroinflammation in retinal degeneration

2020 ◽  
Author(s):  
Xiaowei Sun ◽  
Peng Sun ◽  
Limei Liu ◽  
Pengfei Jiang ◽  
YUANBIN LI
Keyword(s):  
Ferulic Acid ◽  
Retinal Degeneration ◽  
Microglia Activation ◽  
Immunofluorescent Staining ◽  
Inflammatory Factors ◽  
Immunomodulatory Activity ◽  
Ccl2 Expression ◽  
The Impact

Abstract Background : To explore the impact of Ferulic acid (FA) on microglia-mediated neuroinflammation as well as associated retinal degeneration by using a rd10 mouse model as a means. Methods : Rd10 mice received different concentrations of FA treatment every day from postnatal day (P)4 to P24. At P25, mice visual function were detected by electroretinogram, then retinae were collected for further investigation. Retinal microglia activation state and relevant cytokines were evaluated by qPCR, Western blot and immunofluorescent staining. The retinal structure was assessed by HE Staining. Results :50mg/kg FA supplement exhibited optimal protection against retinal degeneration, with treated mice exhibiting more photoreceptor nuclei as well as significant wave amplitude amplification in electroretinograms. FA suppressed microglia activation both in vivo and in vitro , inhibited pro-inflammatory factors Tnfα, IL1β, Ccl2 expression in rd10 retinae. Furthermore, FA suppressed the activation of STAT1 and subsequently IRF8 expression, potentially highlighting a role for these pathways in FA-mediated immunomodulatory activity. Conclusions : Attenuating neuroinflammation by FA may be beneficial to retard retinal degeneration.

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