scholarly journals Chronic mild and acute severe glaucomatous neurodegeneration derived from silicone oil-induced ocular hypertension

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fang Fang ◽  
Jie Zhang ◽  
Pei Zhuang ◽  
Pingting Liu ◽  
Liang Li ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
High Frequency ◽  
Molecular Mechanisms ◽  
Silicone Oil ◽  
Early Time ◽  
Similar Degree ◽  
Pupillary Dilation ◽  
Early Time Point ◽  
Chronic Model ◽  
Iop Elevation

AbstractRecently, we established silicone oil-induced ocular hypertension (SOHU) mouse model with significant glaucomatous neurodegeneration. Here we characterize two additional variations of this model that simulate two distinct glaucoma types. The first is a chronic model produced by high frequency (HF) pupillary dilation after SO-induced pupillary block, which shows sustained moderate IOP elevation and corresponding slow, mild glaucomatous neurodegeneration. We also demonstrate that although SO removal quickly returns IOP to normal, the glaucomatous neurodegeneration continues to advance to a similar degree as in the HF group without SO removal. The second, an acute model created by no pupillary dilation (ND), shows a greatly elevated IOP and severe inner retina degeneration at an early time point. Therefore, by a straightforward dilation scheme, we extend our original SOHU model to recapitulate phenotypes of two major glaucoma forms, which will be invaluable for selecting neuroprotectants and elucidating their molecular mechanisms.

scholarly journals Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective

2017 ◽  
Vol 114 (19) ◽  
pp. E3839-E3848 ◽  
Author(s):  
Jeffrey M. Harder ◽  
Catherine E. Braine ◽  
Pete A. Williams ◽  
Xianjun Zhu ◽  
Katharine H. MacNicoll ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Transcriptional Profiling ◽  
Early Time ◽  
Complement C3 ◽  
Egfr Signaling ◽  
Early Time Point ◽  
Complement Components ◽  
Iop Elevation ◽  
Time Point

Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wlds allele, which protects from axon dysfunction. We demonstrate that DBA/2J.Wlds mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J.Wlds mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J.Wlds mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma.

scholarly journals Silicone oil-induced ocular hypertension and glaucomatous neurodegeneration in mouse

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jie Zhang ◽  
Liang Li ◽  
Haoliang Huang ◽  
Fang Fang ◽  
Hannah C Webber ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Animal Species ◽  
Silicone Oil ◽  
Vitreoretinal Surgery ◽  
Axon Degeneration ◽  
Retinal Ganglion ◽  
Dynamic Changes ◽  
Intracameral Injection ◽  
Iop Elevation ◽  
Selection Of

Understanding the molecular mechanism of glaucoma and development of neuroprotectants is significantly hindered by the lack of a reliable animal model that accurately recapitulates human glaucoma. Here, we sought to develop a mouse model for the secondary glaucoma that is often observed in humans after silicone oil (SO) blocks the pupil or migrates into the anterior chamber following vitreoretinal surgery. We observed significant intraocular pressure (IOP) elevation after intracameral injection of SO, and that SO removal allows IOP to return quickly to normal. This simple, inducible and reversible mouse ocular hypertension model shows dynamic changes of visual function that correlate with progressive retinal ganglion cell (RGC) loss and axon degeneration. It may be applicable with only minor modifications to a range of animal species in which it will generate stable, robust IOP elevation and significant neurodegeneration that will facilitate selection of neuroprotectants and investigating the pathogenesis of ocular hypertension-induced glaucoma.

scholarly journals The Role of microRNAs in the Regulation of Apoptosis in Lung Cancer and Its Application in Cancer Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Norahayu Othman ◽  
Noor Hasima Nagoor
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
High Frequency ◽  
Tumor Suppressor Genes ◽  
Molecular Mechanisms ◽  
Lung Carcinogenesis ◽  
The Past ◽  
Late Stage Diagnosis ◽  
Anticancer Treatment

Lung cancer remains to be one of the most common and serious types of cancer worldwide. While treatment is available, the survival rate of this cancer is still critically low due to late stage diagnosis and high frequency of drug resistance, thus highlighting the pressing need for a greater understanding of the molecular mechanisms involved in lung carcinogenesis. Studies in the past years have evidenced that microRNAs (miRNAs) are critical players in the regulation of various biological functions, including apoptosis, which is a process frequently evaded in cancer progression. Recently, miRNAs were demonstrated to possess proapoptotic or antiapoptotic abilities through the targeting of oncogenes or tumor suppressor genes. This review examines the involvement of miRNAs in the apoptotic process of lung cancer and will also touch on the promising evidence supporting the role of miRNAs in regulating sensitivity to anticancer treatment.

scholarly journals Heavy Silicone Oil and Intraocular Inflammation

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Francesco Morescalchi ◽  
Ciro Costagliola ◽  
Sarah Duse ◽  
Elena Gambicorti ◽  
Barbara Parolini ◽  
...  
Keyword(s):  
Specific Gravity ◽  
Molecular Mechanisms ◽  
Silicone Oil ◽  
Surgical Techniques ◽  
Chemical Properties ◽  
Intraocular Inflammation ◽  
Retinal Breaks ◽  
Oxane Hd ◽  
Long Acting ◽  
Physical And Chemical

In the past two decades, many advances have been made in vitrectomy instrumentation, surgical techniques, and the use of different tamponade agents. These agents serve close retinal breaks, confine eventual retinal redetachment, and prevent proliferative vitreoretinopathy (PVR). Long-acting gases and silicone oil are effective internal tamponade agents; however, because their specific gravity is lower than that of the vitreous fluid, they may provide adequate support for the superior retina but lack efficacy for the inferior retina, especially when the fill is subtotal. Thus, a specific role may exist for an internal tamponade agent with a higher specific gravity, such as heavy silicone oils (HSOs), Densiron 68, Oxane HD, HWS 45-300, HWS 46-3000, and HeavySil. Some clinical evidence seems to presume that heavy tamponades are more prone to intraocular inflammation than standard silicone if they remain in the eye for several months. In this review, we discuss the fundamental clinical and biochemical/molecular mechanisms involved in the inflammatory response after the use of heavy tamponade: toxicity due to impurities or instability of the agent, direct toxicity and immunogenicity, oil emulsification, and mechanical injury due to gravity. The physical and chemical properties of various HSOs and their efficacy and safety profiles are also described.

scholarly journals Spatiotemporal Dynamics of Molecular Pathology in Amyotrophic Lateral Sclerosis

2018 ◽  
Author(s):  
Silas Maniatis ◽  
Tarmo Äijö ◽  
Sanja Vickovic ◽  
Catherine Braine ◽  
Kristy Kang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Molecular Mechanisms ◽  
Early Time ◽  
Spatiotemporal Dynamics ◽  
Course Of Disease ◽  
Molecular Events ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractParalysis occurring in amyotrophic lateral sclerosis (ALS) results from denervation of skeletal muscle as a consequence of motor neuron degeneration. Interactions between motor neurons and glia contribute to motor neuron loss, but the spatiotemporal ordering of molecular events that drive these processes in intact spinal tissue remains poorly understood. Here, we use spatial transcriptomics to obtain gene expression measurements of mouse spinal cords over the course of disease, as well as of postmortem tissue from ALS patients, to characterize the underlying molecular mechanisms in ALS. We identify novel pathway dynamics, regional differences between microglia and astrocyte populations at early time-points, and discern perturbations in several transcriptional pathways shared between murine models of ALS and human postmortem spinal cords.One Sentence SummaryAnalysis of the ALS spinal cord using Spatial Transcriptomics reveals spatiotemporal dynamics of disease driven gene regulation.

Cranioplasty Reverses Dysfunction of the Solutes Distribution in the Brain Parenchyma After Decompressive Craniectomy

Neurosurgery ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 1064-1069 ◽  
Author(s):  
Alin Borha ◽  
Audrey Chagnot ◽  
Romain Goulay ◽  
Evelyne Emery ◽  
Denis Vivien ◽  
...  
Keyword(s):  
Decompressive Craniectomy ◽  
Early Time ◽  
Brain Parenchyma ◽  
Late Time ◽  
Perivascular Spaces ◽  
Early Time Point ◽  
The Impact ◽  
The Brain ◽  
Brain Homeostasis ◽  
Time Point

Abstract Background Solutes distribution by the intracranial cerebrospinal fluid (CSF) fluxes along perivascular spaces and through interstitial fluid (ISF) play a key role in the clearance of brain metabolites, with essential functions in maintaining brain homeostasis. Objective To investigate the impact of decompressive craniectomy (DC) and cranioplasty (CP) on the efficacy of solutes distribution by the intracranial CSF and ISF flux. Methods Mice were allocated in 3 groups: sham surgery, DC, and DC followed by CP. The solutes distribution in the brain parenchyma was assessed using T1 magnetic resonance imaging after injection of DOTA-Gadolinium in the cisterna magna. This evaluation was performed at an early time point following DC (after 2 d) and at a later time point (after 15 d). We evaluated the solutes distribution in the whole brain and in the region underneath the DC area. Results Our results demonstrate that the global solutes distribution in the brain parenchyma is impaired after DC in mice, both at early and late time-points. However, there was no impact of DC on the solutes distribution just under the craniectomy. We then provide evidence that this impairment was reversed by CP. Conclusion The solute distribution in the brain parenchyma by the CSF and ISF is impaired by DC, a phenomenon reversed by CP.

Incidence and Risk Factors of Ocular Hypertension following Pars Plana Vitrectomy and Silicone Oil Injection

2018 ◽  
Vol 240 (3) ◽  
pp. 129-134 ◽  
Author(s):  
Elyse Jabbour ◽  
Georges Azar ◽  
Joelle Antoun ◽  
Hampig Raphael Kourie ◽  
Youssef Abdelmassih ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ocular Hypertension ◽  
Pars Plana Vitrectomy ◽  
Silicone Oil ◽  
Pars Plana ◽  
Oil Injection

Salt induced programmed cell death in rice: evidence from chloroplast proteome signature

2021 ◽  
Vol 48 (1) ◽  
pp. 8
Author(s):  
Vivek Ambastha ◽  
Sudhir K. Sopory ◽  
Baishnab C. Tripathy ◽  
Budhi Sagar Tiwari
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Early Time ◽  
Biological Functions ◽  
Rice Seedlings ◽  
Early Time Point ◽  
Phosphorylation Pattern ◽  
Moderate Salinity ◽  
Chloroplast Proteome ◽  
Time Point

Soil salinity, depending on its intensity, drives a challenged plant either to death, or survival with compromised productivity. On exposure to moderate salinity, plants can often survive by sacrificing some of their cells ‘in target’ following a route called programmed cell death (PCD). In animals, PCD has been well characterised, and involvement of mitochondria in the execution of PCD events has been unequivocally proven. In plants, mechanistic details of the process are still in grey area. Previously, we have shown that in green tissues of rice, for salt induced PCD to occur, the presence of active chloroplasts and light are equally important. In the present work, we have characterised the chloroplast proteome in rice seedlings at 12 and 24 h after salt exposure and before the time point where the signature of PCD was observed. We identified almost 100 proteins from chloroplasts, which were divided in to 11 categories based on the biological functions in which they were involved. Our results concerning the differential expression of chloroplastic proteins revealed involvement of some novel candidates. Moreover, we observed maximum phosphorylation pattern of chloroplastic proteins at an early time point (12 h) of salt exposure.

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