scholarly journals Myosin 1f-mediated activation of microglia contributes to the photoreceptor degeneration in a mouse model of retinal detachment

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Yimin Wang ◽  
Xiaohuan Zhao ◽  
Min Gao ◽  
Xiaoling Wan ◽  
Yinong Guo ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Visual Acuity ◽  
Retinal Detachment ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Vision Loss ◽  
Photoreceptor Degeneration ◽  
Retinal Injury ◽  
Photoreceptor Death

AbstractPhotoreceptor death and neurodegeneration is the leading cause of irreversible vision loss. The inflammatory response of microglia plays an important role in the process of neurodegeneration. In this study, we chose retinal detachment as the model of photoreceptor degeneration. We found Myosin 1f was upregulated after retinal detachment, and it was specifically expressed in microglia. Deficiency of myosin 1f protected against photoreceptor apoptosis by inhibiting microglia activation. The elimination of microglia can abolish the protective effect of myosin 1f deficiency. After stimulation by LPS, microglia with myosin 1f deficiency showed downregulation of the MAPK and AKT pathways. Our results demonstrated that myosin 1f plays a crucial role in microglia-induced neuroinflammation after retinal injury and photoreceptor degeneration by regulating two classic inflammatory pathways and thereby decreasing the expression of inflammatory cytokines. Knockout of myosin 1f reduces the intensity of the immune response and prevents cell death of photoreceptor, suggesting that myosin 1f can be inhibited to prevent a decline in visual acuity after retinal detachment.

scholarly journals Myosin 1f-mediated Activation of Microglia Contributes to the Photoreceptor Degeneration in a Mouse Model of Retinal Detachment

2020 ◽  
Author(s):  
Yimin Wang ◽  
Xiaohuan Zhao ◽  
Min Gao ◽  
Xiaoling Wan ◽  
Yinong Guo ◽  
...  
Keyword(s):  
Retinal Detachment ◽  
Mouse Model ◽  
Cell Activation ◽  
Vision Loss ◽  
Immune Cell ◽  
Tunel Staining ◽  
Photoreceptor Degeneration ◽  
Immune Cell Activation ◽  
Retinal Injury ◽  
Neuro Inflammation

Abstract Background: Photoreceptor death and neurodegeneration is the leading cause of irreversible vision loss. The inflammatory response of microglia plays an important role in the process of neurodegeneration. In this study, we examined the involvement of myosin 1f as a key regulator of immune cell activation via the AKT and MAPK pathways in microglia. Methods: We chose retinal detachment as the model of photoreceptor degeneration. Immunofluorescence and Western Blot was performed to confirm the expression and location of myosin 1f in detached retina. The RD mouse model was induced in WT and myosin 1f-/- mice and confirmed by HE and TUNEL staining. The expression of inflammatory cytokine and downstream pathways was assessed via qPCR and WB.Results: Myosin 1f was upregulated after retinal detachment, and it was specifically expressed in microglia. Deficiency of myosin 1f protected against cell death by inhibiting microglia activation. The elimination of microglia can abolish the protective effect of myosin 1f deficiency. After stimulation by LPS, microglia with myosin 1f deficiency showed downregulation of the MAPK and AKT pathways.Conclusions: Myosin 1f plays a crucial role in microglia-induced neuro-inflammation after retinal injury and photoreceptor degeneration by regulating 2 classic pathways, MAPK and AKT, and thereby decreasing the expression of inflammatory cytokines. Myosin 1f can be inhibited to prevent a decline in visual acuity after photoreceptor degeneration.

scholarly journals Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Salvatore Di Lauro ◽  
Melissa Castrejón ◽  
Itziar Fernández ◽  
Jimena Rojas ◽  
Rosa M. Coco ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Retinal Detachment ◽  
Visual Loss ◽  
Vision Loss ◽  
Multicentric Study ◽  
Prospective Multicentre Study ◽  
Snellen Chart ◽  
Pars Plana ◽  
Phakic Eyes

Purpose. To quantify the frequency of visual loss after successful retinal detachment (RD) surgery in macula-on patients in a multicentric, prospective series of RD.Methods. Clinical variables from consecutive macula-on RD patients were collected in a prospective multicentric study. Visual loss was defined as at least a reduction in one line in best corrected visual acuity (VA) with Snellen chart. The series were divided into 4 subgroups: (1) all macula-on eyes (n=357); (2) macula-on patients with visual loss at the third month of follow-up (n=53) which were further subdivided in (3) phakic eyes (n=39); and (4) pseudophakic eyes (n=14).Results. Fifty-three eyes (14.9%) had visual loss three months after surgery (n=39phakic eyes;n=14pseudophakic eyes). There were no statistically significant differences between them regarding their clinical characteristics. Pars plana vitrectomy (PPV) was used in 67.2% of cases, scleral buckle in 57.7%, and scleral explant in 11.9% (36.1% were combined procedures).Conclusions. Around 15% of macula-on RD eyes lose VA after successful surgery. Development of cataracts may be one cause in phakic eyes, but vision loss in pseudophakic eyes could have other explanations such as the effect of released factors produced by retinal ischemia on the macula area. Further investigations are necessary to elucidate this hypothesis.

To the question of retinal detachment in cytomegalovirus uveitis in HIV-infected patients: treatment outcomes

2021 ◽  
pp. 17-19
Author(s):  
T.D. Sizova ◽  
◽  
V.M. Khokkanen ◽  
F.O. Kasymov ◽  
E.V. Boyko ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Retinal Detachment ◽  
Hiv Infection ◽  
Vision Loss ◽  
Acute Retinal Necrosis ◽  
Study Group ◽  
Ophthalmological Examination ◽  
Complex Treatment ◽  
Key Words Cytomegalovirus ◽  
Common Causes

Cytomegalovirus uveitis (CMV-uveitis) is one of the most common causes of vision loss in HIV-infected patients. The purpose is to characterize the clinical features of the course of retinal detachment in HIV infection. Material and methods. The study group included 29 patients, 34 eyes (9 men and 20 women). All patients underwent a standard routine ophthalmological examination. To confirm the diagnosis, an ultrasound of the eyeball was performed. Results. The following forms of retinal detachment were identified: acute retinal necrosis, regmatogenic and traction detachment. In 50% of cases, the disease occurred as acute retinal necrosis of CMV-etiology. Visual acuity in the group of patients with operated retinal detachment became significantly lower after complex treatment. Conclusions. CMV-uveitis has a chronic sluggish course, despite multicomponent treatment. Key words: cytomegalovirus, uveitis, HIV, HIV-infection, AIDS, retinal detachment.

scholarly journals Loss of αA or αB-Crystallin Accelerates Photoreceptor Cell Death in a Mouse Model of P23H Autosomal Dominant Retinitis Pigmentosa

2021 ◽  
Vol 23 (1) ◽  
pp. 70
Author(s):  
Tiantian Wang ◽  
Jingyu Yao ◽  
Lin Jia ◽  
Patrice E. Fort ◽  
David N. Zacks
Keyword(s):  
Cell Death ◽  
Mouse Model ◽  
Unfolded Protein ◽  
Retinal Degenerations ◽  
Light Sensing ◽  
Cell Death Pathways ◽  
Αb Crystallin ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Photoreceptor Death

Inherited retinal degenerations (IRD) are a leading cause of visual impairment and can result from mutations in any one of a multitude of genes. Mutations in the light-sensing protein rhodopsin (RHO) is a leading cause of IRD with the most common of those being a missense mutation that results in substitution of proline-23 with histidine. This variant, also known as P23H-RHO, results in rhodopsin misfolding, initiation of endoplasmic reticulum stress, the unfolded protein response, and activation of cell death pathways. In this study, we investigate the effect of α-crystallins on photoreceptor survival in a mouse model of IRD secondary to P23H-RHO. We find that knockout of either αA- or αB-crystallin results in increased intraretinal inflammation, activation of apoptosis and necroptosis, and photoreceptor death. Our data suggest an important role for the ⍺-crystallins in regulating photoreceptor survival in the P23H-RHO mouse model of IRD.

scholarly journals Retinal Detachment After Cataract Surgery and Posterior Laser Capsulotomy in a Young Healthy Male Patient: Case Report

2020 ◽  
pp. 1-3
Author(s):  
Marco Zeppieri ◽  
Marco Zeppieri
Keyword(s):  
Risk Factors ◽  
Visual Acuity ◽  
Retinal Detachment ◽  
Cataract Surgery ◽  
Intraocular Lens ◽  
Vision Loss ◽  
Nuclear Cataract ◽  
Cataract Formation ◽  
Laser Treatments ◽  
Visual Acuity Loss

Background: The onset of cataract formation is normally experienced in senile age. The process of lens opacification can also be influenced by other factors, including systemic diseases, infection, trauma, medication, ultraviolet light exposure, genetic predisposition and environmental sources. Gradual vision loss accompanied by a myopic refractive shift can be caused by nuclear cataract formation, even in young patients. Phacoemulsification cataract removal and intraocular lens insertion surgery is indicated when visual acuity loss and/or myopic anisometropia becomes a problem. Surgical and laser treatments are risk factors in developing retinal detachment, especially in myopic patients. Case Presentation: This is a case of an early onset nuclear cataract in a young male. A 44-year-old man visited the hospital complaining of gradual vision loss in his right eye. History study revealed no systemic or ophthalmic diseases or trauma. The patient underwent phacoemulsification nuclear cataract removal and intraocular lens insertion surgery in his right eye, followed by Nd:YAG laser posterior capsulotomy 3 years later. He underwent phacoemulsification nuclear cataract surgery in his left eye at the age of 48 years, followed by laser capsulotomy treatment 2 years later. At the age 50, a routine eye examination revealed retinal detachment in his right eye. He underwent vitrectomy surgery twice. Conclusion: Nuclear lens opacification is seldom of clinical importance in young healthy adult patients; however, it can be the cause of progressive visual acuity loss, especially in the presence of a myopic refractive shift. Surgery, laser treatment and myopia are all risk factors in retinal detachment. This case shows that thorough and periodic routine eye examinations are a must when dealing with patients with unexpected and atypical signs and symptoms, especially having underwent surgery and laser treatments.

scholarly journals SARS-CoV-2 induces inflammasome-dependent pyroptosis and downmodulation of HLA-DR in human monocytes

2020 ◽  
Author(s):  
André C. Ferreira ◽  
Vinicius Cardoso Soares ◽  
Isaclaudia G. de Azevedo-Quintanilha ◽  
Suelen da Silva Gomes Dias ◽  
Natalia Fintelman-Rodrigues ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Response ◽  
Inflammatory Cell ◽  
Viral Infections ◽  
Relevant Information ◽  
Inflammasome Activation ◽  
Human Monocytes ◽  
Hla Dr

AbstractInfection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with leukopenia and uncontrolled inflammatory response in critically ill patients. A better comprehension of SARS-CoV-2-induced monocyte death is essential for the identification of therapies capable to control the hyper-inflammation and reduce viral replication in patients with COVID-19. Here, we show that SARS-CoV-2 induces inflammasome activation and cell death by pyroptosis in human monocytes, experimentally infected and from patients under intensive care. Pyroptosis was dependent on caspase-1 engagement, prior to IL-1ß production and inflammatory cell death. Monocytes exposed to SARS-CoV-2 downregulate HLA-DR, suggesting a potential limitation to orchestrate the immune response. Our results originally describe mechanisms by which monocytes, a central cellular component recruited from peripheral blood to respiratory tract, succumb to control severe 2019 coronavirus disease (COVID-19).Author summarySince its emergence in China in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide. Currently, the number of individuals infected with SARS-CoV-2 and in need of antiviral, anti-inflammatory, anticoagulant and more invasive treatments has overwhelmed the health systems worldwide. In our study, we found that SARS-CoV-2 is capable of inducing inflammatory cell death in human monocytes, one of the main cell types responsible for anti-SARS-CoV-2 immune response. As a consequence of this intracellular inflammatory mechanism (inflammasome engagement), an exacerbated production of inflammatory mediators occurs. The infection also decreases the expression of HLA-DR in monocytes, a molecule related to the orchestration of the immune response in case of viral infections. We also demonstrated that the HIV-1 protease inhibitor, atazanavir (ATV), prevented the uncontrolled inflammatory response, cell death and reduction in HLA-DR expression in SARS-CoV-2-infected monocytes. Our study provides relevant information on the effects of SARS-CoV-2 infection on human monocytes, as well as on the effect of ATV in preventing these pathological effects on the host.

scholarly journals Transcriptomic Analysis of Human Retinal Detachment Reveals Both Inflammatory Response and Photoreceptor Death

PLoS ONE ◽  
2011 ◽  
Vol 6 (12) ◽  
pp. e28791 ◽  
Author(s):  
Marie-Noëlle Delyfer ◽  
Wolfgang Raffelsberger ◽  
David Mercier ◽  
Jean-François Korobelnik ◽  
Alain Gaudric ◽  
...  
Keyword(s):  
Retinal Detachment ◽  
Inflammatory Response ◽  
Transcriptomic Analysis ◽  
Photoreceptor Death

Inhibition of the kinase ITK in a mouse model of asthma reduces cell death and fails to inhibit the inflammatory response

2015 ◽  
Vol 8 (405) ◽  
pp. ra122-ra122 ◽  
Author(s):  
Yonglian Sun ◽  
Ivan Peng ◽  
Joshua D. Webster ◽  
Eric Suto ◽  
Justin Lesch ◽  
...  
Keyword(s):  
Cell Death ◽  
Inflammatory Response ◽  
Mouse Model

scholarly journals RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Yuting Meng ◽  
Qiong Zhang ◽  
Kaihang Wang ◽  
Xujun Zhang ◽  
Rongwei Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Severe Acute Respiratory Syndrome ◽  
Programmed Cell Death ◽  
Inflammatory Response ◽  
Disease Severity ◽  
Biological Processes ◽  
Underlying Mechanisms ◽  
Microarray Analyses

AbstractSevere coronavirus disease 2019 (COVID-19) is characterized by symptoms of lymphopenia and multiorgan damage, but the underlying mechanisms remain unclear. To explore the function of N6-methyladenosine (m6A) modifications in COVID-19, we performed microarray analyses to comprehensively characterize the m6A epitranscriptome. The results revealed distinct global m6A profiles in severe and mild COVID-19 patients. Programmed cell death and inflammatory response were the major biological processes modulated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further, RBM15, a major m6A methyltransferase, was significantly elevated and positively correlated with disease severity. Silencing RBM15 drastically reduced lymphocyte death in vitro. Knockdown of RBM15 remarkably suppressed the expression levels of multitarget genes related to programmed cell death and inflammatory response. This study shows that SARS-CoV-2 infection alters the m6A epitranscriptome of lymphocytes, particularly in the case of severe patients. RBM15 regulated host immune response to SARS-CoV-2 by elevating m6A modifications of multitarget genes. These findings indicate that RBM15 can serve as a target for the treatment of COVID-19.

scholarly journals SARM1 depletion rescues NMNAT1 dependent photoreceptor cell death and retinal degeneration

2020 ◽  
Author(s):  
Yo Sasaki ◽  
Hiroki Kakita ◽  
Shunsuke Kubota ◽  
Abdoulaye Sene ◽  
Tae Jun Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinal Degeneration ◽  
Photoreceptor Cell ◽  
Vision Loss ◽  
Adult Mice ◽  
Conditional Deletion ◽  
Cell Death Pathway ◽  
Human Pathology ◽  
Essential Function ◽  
Photoreceptor Death

AbstractLeber congenital amaurosis type 9 is an autosomal recessive retinopathy caused by mutations of the NAD+ synthesis enzyme NMNAT1. Despite the ubiquitous expression of NMNAT1, patients do not manifest pathologies other than retinal degeneration. Here we demonstrate that widespread NMNAT1 depletion in adult mice mirrors the human pathology, with selective loss of photoreceptors highlighting the exquisite vulnerability of these cells to NMNAT1 loss. Conditional deletion demonstrates that NMNAT1 is required within the photoreceptor. Mechanistically, loss of NMNAT1 activates the NADase SARM1, the central executioner of axon degeneration, to trigger photoreceptor death and vision loss. Hence, the essential function of NMNAT1 in photoreceptors is to inhibit SARM1, highlighting an unexpected shared mechanism between axonal degeneration and photoreceptor neurodegeneration. These results define a novel SARM1-dependent photoreceptor cell death pathway and identifies SARM1 as a therapeutic candidate for retinopathies.

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