Tributary vein obstruction pathogenesis and treatment of sequelae

Archer, D. B.

doi:10.1007/bf00155046

Cited by 18 publications

(8 citation statements)

References 25 publications

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“…This phenomenon contributes to various clinical problems after stroke, myocardial infarction, shock, and organ transplantation. Emerging evidence suggests that IR injury is also implicated in the pathogenesis of several vision-threatening ophthalmic disorders, such as retinal vascular occlusive disease, glaucoma and diabetic retinopathy [1]–[3]. The postulated pathophysiologic mechanisms of ischemic cell injury include depletion of adenosine triphosphate (ATP) and disturbance of intracellular calcium homeostasis, which results in cell death [4].…”

Section: Introductionmentioning

confidence: 99%

The Protective Effects of the Proteasome Inhibitor Bortezomib (Velcade) on Ischemia-Reperfusion Injury in the Rat Retina

Chen

Yang

2013

PLoS ONE

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PurposeTo evaluate the protective effects of bortezomib (Velcade) on ischemia-reperfusion (IR) injury in the rat retina.MethodsThe rats were randomized to receive treatment with saline, low-dose bortezomib (0.05 mg/kg), or high-dose bortezomib (0.2 mg/kg) before the induction of IR injury. Electroretinography (ERG) was used to assess functional changes in the retina. The expression of inflammatory mediators (iNOS, ICAM-1, MCP-1, TNF-α), anti-oxidant proteins (heme oxygenase, thioredoxin, peroxiredoxin), and pro-apoptotic proteins (p53, bax) were quantified by PCR and western blot analysis. An immunofluorescence study was performed to detect the expression of iNOS, oxidative markers (nitrotyrosine, 8-OHdG, acrolein), NF-κB p65, and CD 68. Apoptosis of retinal cells was labeled with in situ TUNEL staining. Neu-N staining was performed in the flat-mounted retina to evaluate the density of retinal ganglion cells.ResultsERG showed a decreased b-wave after IR injury, and pretreatment with bortezomib, especially the high dosage, reduced the functional impairment. Bortezomib successfully reduced the elevation of inflammatory mediators, anti-oxidant proteins, pro-apoptotic proteins and oxidative markers after IR insult in a dose-dependent manner. In a similar fashion, NF-κB p65- and CD 68-positive cells were decreased by bortezomib treatment. Retinal cell apoptosis in each layer was attenuated by bortezomib. The retinal ganglion cell density was markedly decreased in the saline and low-dose bortezomib groups but was not significantly changed in the high-dose bortezomib group.ConclusionsBortezomib had a neuro-protective effect in retinal IR injury, possibly by inhibiting the activation of NF-κB related to IR insult and reducing the inflammatory signals and oxidative stress in the retina.

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Section: Introductionmentioning

confidence: 99%

The Protective Effects of the Proteasome Inhibitor Bortezomib (Velcade) on Ischemia-Reperfusion Injury in the Rat Retina

Chen

Yang

2013

PLoS ONE

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“…The current treatment for brain stroke is largely limited to thrombolysis with tissue plasminogen activator, but only about 5% of stroke patients have the opportunity to receive this thrombolysis treatment2. Retinal ischemia has been proposed to contribute to the pathologies of several retinal diseases, including diabetic retinopathy, optic neuropathy, glaucoma, and retinal artery occlusion, and is an important cause of blindness345. No treatment effectively protects neurons from the ischemia of such diseases.…”

mentioning

confidence: 99%

KUS121, a VCP modulator, attenuates ischemic retinal cell death via suppressing endoplasmic reticulum stress

Hata

Ikeda

Kikkawa

et al. 2017

Sci Rep

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Ischemic neural damages cause several devastating diseases, including brain stroke and ischemic retinopathies, and endoplasmic reticulum (ER) stress has been proposed to be the underlying mechanism of the neuronal cell death of these conditions. We previously synthesized Kyoto University substances (KUSs) as modulators of valosin-containing protein (VCP); KUSs inhibit VCP ATPase activity and protect cells from different cell death-inducing insults. Here, we examined the efficacy of KUS121 in a rat model of retinal ischemic injury. Systemic administration of KUS121 to rats with ischemic retinal injury significantly suppressed inner retinal thinning and death of retinal ganglion and amacrine cells, with a significant functional maintenance of visual functions, as judged by electroretinography. Furthermore, intravitreal injection of KUS121, which is the clinically preferred route of drug administration for retinal diseases, appeared to show an equal or better neuroprotective efficacy in the ischemic retina compared with systemic administration. Indeed, induction of the ER stress marker C/EBP homologous protein (CHOP) after the ischemic insult was significantly suppressed by KUS121 administration. Our study suggests VCP modulation by KUS as a promising novel therapeutic strategy for ischemic neuronal diseases.

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“…O cular ischemia plays an important role in the pathophysiology of various ocular diseases such as diabetic retinopathy, 1,2 retinal vascular occlusion, 3 anterior optic neuropathy, 4 and possibly glaucoma. [5][6][7] It may ultimately lead to neuronal death by inducing apoptosis 8 or necrosis.…”

mentioning

confidence: 99%

Quantification of Ischemic Damage in the Rat Retina: A Comparative Study Using Evoked Potentials, Electroretinography, and Histology

Jehle¹,

Wingert²,

Dimitriu³

et al. 2008

Invest. Ophthalmol. Vis. Sci.

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Tributary vein obstruction pathogenesis and treatment of sequelae

Cited by 18 publications

References 25 publications

The Protective Effects of the Proteasome Inhibitor Bortezomib (Velcade) on Ischemia-Reperfusion Injury in the Rat Retina

The Protective Effects of the Proteasome Inhibitor Bortezomib (Velcade) on Ischemia-Reperfusion Injury in the Rat Retina

KUS121, a VCP modulator, attenuates ischemic retinal cell death via suppressing endoplasmic reticulum stress

Quantification of Ischemic Damage in the Rat Retina: A Comparative Study Using Evoked Potentials, Electroretinography, and Histology

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