scholarly journals Inactivation of Endothelial ADAM17 Reduces Retinal Ischemia-Reperfusion Induced Neuronal and Vascular Damage

2020 ◽  
Vol 21 (15) ◽  
pp. 5379
Author(s):  
Diana R Gutsaeva ◽  
Lamiaa Shalaby ◽  
Folami L Powell ◽  
Menaka C Thounaojam ◽  
Hossameldin Abouhish ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Cell Loss ◽  
Retinal Ischemia ◽  
Retinal Cell ◽  
Contralateral Eye ◽  
A Disintegrin And Metalloproteinase ◽  
Retinal Thinning ◽  
Capillary Degeneration ◽  
And Control

Retinal ischemia contributes to visual impairment in ischemic retinopathies. A disintegrin and metalloproteinase ADAM17 is implicated in multiple vascular pathologies through its ability to regulate inflammatory signaling via ectodomain shedding. We investigated the role of endothelial ADAM17 in neuronal and vascular degeneration associated with retinal ischemia reperfusion (IR) injury using mice with conditional inactivation of ADAM17 in vascular endothelium. ADAM17Cre-flox and control ADAM17flox mice were subjected to 40 min of pressure-induced retinal ischemia, with the contralateral eye serving as control. Albumin extravasation and retinal leukostasis were evaluated 48 h after reperfusion. Retinal morphometric analysis was conducted 7 days after reperfusion. Degenerate capillaries were assessed by elastase digest and visual function was evaluated by optokinetic test 14 and 7 days following ischemia, respectively. Lack of ADAM17 decreased vascular leakage and reduced retinal thinning and ganglion cell loss in ADAM17Cre-flox mice. Further, ADAM17Cre-flox mice exhibited a remarkable reduction in capillary degeneration following IR. Decrease in neurovascular degeneration in ADAM17Cre-flox mice correlated with decreased activation of caspase-3 and was associated with reduction in oxidative stress and retinal leukostasis. In addition, knockdown of ADAM17 resulted in decreased cleavage of p75NTR, the process known to be associated with retinal cell apoptosis. A decline in visual acuity evidenced by decrease in spatial frequency threshold observed in ADAM17flox mice was partially restored in ADAM17-endothelial deficient mice. The obtained results provide evidence that endothelial ADAM17 is an important contributor to IR-induced neurovascular damage in the retina and suggest that interventions directed at regulating ADAM17 activity can be beneficial for alleviating the consequences of retinal ischemia.

Deleterious Role of TNF-α in Retinal Ischemia–Reperfusion Injury

2008 ◽  
Vol 49 (8) ◽  
pp. 3605 ◽  
Author(s):  
Samuel Berger ◽  
Sean I. Savitz ◽  
Sheetal Nijhawan ◽  
Manjeet Singh ◽  
Joel David ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Retinal Ischemia ◽  
Tnf Α

Deleterious Role of Anti-high Mobility Group Box 1 Monoclonal Antibody in Retinal Ischemia-reperfusion Injury

2011 ◽  
Vol 36 (11) ◽  
pp. 1037-1046 ◽  
Author(s):  
Shenyang Yang ◽  
Kazuyuki Hirooka ◽  
Ye Liu ◽  
Tomoyoshi Fujita ◽  
Kouki Fukuda ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Mobility ◽  
Retinal Ischemia ◽  
High Mobility Group

Abstract 339: Heterozygous Disruption of Drp1 Enhances Myocardial Injury in Response to Ischemia/Reperfusion via Inhibition of Mitophagy

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Yoshiyuki Ikeda ◽  
Peiyong Zhai ◽  
Mitsuru Ohishi ◽  
Junichi Sadoshima
Keyword(s):  
Stress Resistance ◽  
Myocardial Injury ◽  
Essential Role ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Area At Risk ◽  
Electron Microscopic ◽  
Mitochondrial Mass ◽  
And Control

Mitochondrial fission and fusion are essential for maintaining mitochondrial quality control. However, their role in stress resistance remains unknown. Since Dynamin-related protein 1 (Drp1) plays an essential role in mediating mitochondrial fission, we used cardiac-specific heterozygous Drp1 KO (Drp1-hetCKO) mice whose cardiac function is normal at 12 weeks of age. In order to evaluate the role of Drp1 in mediating stress resistance, 12-week-old Drp1-hetCKO and control (Ctr) mice were subjected to myocardial ischemia (30 min)/reperfusion (24 hours) (I/R). I/R injury increased the translocation of Drp1 from cytosol to mitochondria in Ctr mice, whereas this translocation was attenuated in Drp1-hetCKO mice.The infarct size/area at risk after I/R was significantly greater in Drp-1 hetero KO mice than in control mice (55.2 ± 3.0 vs. 40.2 ± 1.6%). Electron microscopic analyses showed that I/R significantly decreased mitochondrial mass and increased the number of autophagosomes containing mitochondria in control mice. However, these changes were significantly attenuated in Drp1-hetCKO mice, suggesting that endogenous Drp1 mediates mitochondrial fission and mitophagy after I/R (Relative mitochondrial mass, Ctr, baseline: 1.0±0.3, I/R: 0.7±0.4; Drp1-hetCKO, baseline: 1.8±0.3, I/R: 1.7±0.3). We also examined mitophagy using mitochondria-targeted Keima fluorescence. Keima has a bimodal excitation spectrum peaking at 440 and 560 nm, corresponding to the neutral and acidic pH states, respectively. The maturation of autophagosomes to autolysosomes can be monitored by measuring the fluorescence of mitochondria-targeted Keima. Fluorescent dots with high ratios of 560/440, indicating mitophagy, were significantly increased after GD in sh-scramble-transduced CMs (GD: 28.6±4.2, control 2.3±1.0 dots/cell, p<0.01) but not in sh-Drp1-transduced CMs (GD: 2.4±1.8, control 3.2±1.6 dots/cell, not significant), suggesting that GD stimulates mitophagy but that this is inhibited when Drp-1 is downregulated. These results suggest that endogenous Drp1 play an essential role in mediating mitochondrial fission and mitophagy, which in turn play an essential role in mediating myocardial protection in response to I/R.

scholarly journals Nrf2 has a protective role against neuronal and capillary degeneration in retinal ischemia–reperfusion injury

2011 ◽  
Vol 51 (1) ◽  
pp. 216-224 ◽  
Author(s):  
Yanhong Wei ◽  
Junsong Gong ◽  
Takeshi Yoshida ◽  
Charles G. Eberhart ◽  
Zhenhua Xu ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Retinal Ischemia ◽  
Capillary Degeneration

scholarly journals A Novel HIF Inhibitor Halofuginone Prevents Neurodegeneration in a Murine Model of Retinal Ischemia-Reperfusion

2019 ◽  
Vol 20 (13) ◽  
pp. 3171 ◽  
Author(s):  
Hiromitsu Kunimi ◽  
Yukihiro Miwa ◽  
Hiroyoshi Inoue ◽  
Kazuo Tsubota ◽  
Toshihide Kurihara
Keyword(s):  
Intraocular Pressure ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Hypoxia Inducible Factor ◽  
Retinal Ischemia ◽  
In Vitro Screening ◽  
Degenerative Diseases ◽  
Retinal Degenerative Diseases

Neurodegeneration caused with retinal ischemia or high intraocular pressure is irreversible in general. We have focused on the role of hypoxia-inducible factor (HIF) in retinal homeostasis and revealed that HIF inhibition may be effective against retinal neovascular and neurodegeneration. In this study, we performed in vitro screening of natural products and found halofuginone, which is a derivative of febrifugine extracted from hydrangea, as a novel HIF inhibitor. Administration of halofuginone showed a significant neuroprotective effect by inhibiting HIF-1α expression in a murine retinal ischemia-reperfusion model histologically and functionally. These results indicate that halofuginone can be a neuroprotective agent in ischemic retinal degenerative diseases.

Morphogenesis of a New Human Herpes-Type Virus Isolate (Sasha Virus)

1973 ◽  
Vol 31 ◽  
pp. 592-593
Author(s):  
R. F. Zeigel ◽  
W. Munyon
Keyword(s):  
Virus Isolate ◽  
Calf Serum ◽  
Uranyl Acetate ◽  
Human Herpes ◽  
Human Embryonic Lung ◽  
Human Herpes Virus ◽  
Intracytoplasmic Inclusions ◽  
Hel Cells ◽  
And Control

In continuing studies on the role of viruses in biochemical transformation, Dr. Munyon has succeeded in isolating a highly infectious human herpes virus. Fluids of buccal pustular lesions from Sasha Munyon (10 mo. old) uiere introduced into monolayer sheets of human embryonic lung (HEL) cell cultures propagated in Eagles’ medium containing 5% calf serum. After 18 hours the cells exhibited a dramatic C.P.E. (intranuclear vacuoles, peripheral patching of chromatin, intracytoplasmic inclusions). Control HEL cells failed to reflect similar changes. Infected and control HEL cells were scraped from plastic flasks at 18 hrs. of incubation and centrifuged at 1200 × g for 15 min. Resultant cell packs uiere fixed in Dalton's chrome osmium, and post-fixed in aqueous uranyl acetate. Figure 1 illustrates typical hexagonal herpes-type nucleocapsids within the intranuclear virogenic regions. The nucleocapsids are approximately 100 nm in diameter. Nuclear membrane “translocation” (budding) uias observed.

Effects of carbamylcholine on chick embryo aggregate retina cell cultures

1988 ◽  
Vol 46 ◽  
pp. 350-351
Author(s):  
Glenn M. Cohen ◽  
Radharaman Ray
Keyword(s):  
Cell Cultures ◽  
Single Cells ◽  
Retinal Cell ◽  
Cell Aggregates ◽  
High Concentration ◽  
In Ovo ◽  
Sterile Culture ◽  
Retinal Tissue ◽  
Synaptic Junctions ◽  
And Control

Retinal,cell aggregates develop in culture in a pattern similar to the in ovo retina, forming neurites first and then synapses. In the present study, we continuously exposed chick retinal cell aggregates to a high concentration (1 mM) of carbamylcholine (carbachol), an acetylcholine (ACh) analog that resists hydrolysis by acetylcholinesterase (AChE). This situation is similar to organophosphorus anticholinesterase poisoning in which the ACh level is elevated at synaptic junctions due to inhibition of AChE, Our objective was to determine whether continuous carbachol exposure either damaged cholino- ceptive neurites, cell bodies, and synaptic elements of the aggregates or influenced (hastened or retarded) their development.The retinal tissue was isolated aseptically from 11 day embryonic White Leghorn chicks and then enzymatically (trypsin) and mechanically (trituration) dissociated into single cells. After washing the cells by repeated suspension and low (about 200 x G) centrifugation twice, aggregate cell cultures (about l0 cells/culture) were initiated in 1.5 ml medium (BME, GIBCO) in 35 mm sterile culture dishes and maintained as experimental (containing 10-3 M carbachol) and control specimens.

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