Interleukin-1β Mediates Ischemic Injury in the Rat Retina

Yoneda, Shinji; Tanihara, Hidenobu; Kido, Noriaki; Honda, Yoshio; Goto, Wakana; Hara, Hideaki; Miyawaki, Nobuaki

doi:10.1006/exer.2001.1072

Cited by 104 publications

(74 citation statements)

References 42 publications

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“…Moreover, like diabetic retinopathy, retinopathy induced by I/R causes up-regulation of NOS2, COX-2, and IL-1 (39,44,46), and therapeutic approaches that inhibit development of diabetic retinopathy in animals (blockade or inhibition of the expression of NOS2, TNF-␣, and IL-1) likewise inhibit the retinal pathology after I/R (7,39,44,46,47). These overlapping features between diabetic and I/R-induced retinopathies raise the possibility that CD40 is a mediator also of diabetic retinopathy.…”

Section: Discussionmentioning

confidence: 99%

“…The rapid expression of IL-1 after ischemia and the role of this cytokine in chemokine secretion and tissue injury (44,45,58) provided rationale for exploring whether CD40 and IL-1 cooperate to produce KC/CXCL1 by retinal cells. We report that CD40 stimulation of retinal endothelial cells in the presence of IL-1␤ results in a marked increase in production of KC/CXCL1.…”

Section: Discussionmentioning

confidence: 99%

“…Next, we examined the effects of CD40 stimulation on KC/CXCL1 secretion. IL-1 is an important proinflammatory cytokine induced after ischemia that regulates chemokine production and mediates tissue injury (44,45). We explored whether CD40 and IL-1 cooperate to induce KC/CXCL1 production.…”

Section: Cd40 Induces Icam-1 Up-regulation As Well As Kc/cxcl1 Producmentioning

confidence: 99%

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CD40 Mediates Retinal Inflammation and Neurovascular Degeneration

Portillo

Grol

Zheng

et al. 2008

The Journal of Immunology

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Retinopathies are major causes of visual impairment. We used a model of ischemic retinopathy to examine the role of CD40 in the pathogenesis of retinal injury. Retinal inflammation, loss of ganglion cells, and capillary degeneration were markedly attenuated in ischemic retinas of CD40−/− mice. Up-regulation of NOS2 and COX2 after retinal ischemia were blunted in CD40−/− mice. NOS2-COX-2 up-regulation in ischemic retinas from wild-type mice was at least in part explained by recruitment of NOS2+COX-2+ leukocytes. Up-regulation of KC/CXCL1 and ICAM-1 also required CD40. Retinal endothelial and Muller cells expressed CD40. Stimulation of these cells through CD40 caused ICAM-1 up-regulation and KC/CXCL1 production. Bone marrow transplant experiments revealed that leukocyte infiltration, ganglion cell loss, and up-regulation of proinflammatory molecules after retinal ischemia were dependent on CD40 expression in the retina and not peripheral blood leukocytes. These studies identified CD40 as a regulator of retinal inflammation and neurovascular degeneration. They support a model in which CD40 stimulation of endothelial and Muller cells triggers adhesion molecule up-regulation and chemokine production, promoting the recruitment of leukocytes that express NOS2/COX-2, molecules linked to neurovascular degeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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CD40 Mediates Retinal Inflammation and Neurovascular Degeneration

Portillo

Grol

Zheng

et al. 2008

The Journal of Immunology

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“…Recent studies have demonstrated that inflammasomes have a key role in the processing of IL-1β, impacting the course of CNS infection, autoimmune disease, and injury (26)(27)(28). However, the potential role of inflammasomes in IOP-induced RGC death has not been explored.…”

Section: Nlrp1 and Nlrp3 Inflammasomes Are Activated By Tlr4 Signalingmentioning

confidence: 99%

Caspase-8 promotes NLRP1/NLRP3 inflammasome activation and IL-1β production in acute glaucoma

Chi

Chen

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

254

222

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Acute glaucoma is a sight-threatening condition characterized by a sudden and substantial rise in intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Angle closure glaucoma, a common cause of glaucoma in Asia that affects tens of millions of people worldwide, often presents acutely with loss of vision, pain, and high IOP. Even when medical and surgical treatment is available, acute angle closure glaucoma can cause permanent and irreversible loss of vision. Toll-like receptor 4 (TLR4) signaling has been previously implicated in the pathogenesis of IOP-induced RGC death, although the underlying mechanisms are largely unknown. In the present study, we used an acute IOP elevation/glaucoma model to investigate the underlying mechanism of RGC death. We found that TLR4 leads to increased caspase-8 expression; this elevation increases IL-1β expression and RGC death via a caspase-1-dependent pathway involving Nod-like receptor family, pyrin domain containing 1 (NLRP1)/NLRP3 inflammasomes and a caspase-1-independent pathway. We show that inhibition of caspase-8 activation significantly attenuates RGC death by down-regulating the activation of NLRP1 and NLRP3, thus demonstrating the pivotal role of caspase-8 in the TLR4-mediated activation of inflammasomes. These findings demonstrate collectively a critical role of caspase-8 in transducing TLR4-mediated IL-1β production and RGC death and highlight signal transduction in a caspase-1-dependent NLRP1/NLRP3 inflammasome pathway and a caspase-1-independent pathway in acute glaucoma. These results provide new insight into the pathogenesis of glaucoma and point to a treatment strategy.retinal ischemia/reperfusion injury | cell apoptosis A cute glaucoma is a significant cause of permanent vision loss and irreversible blindness worldwide (1). It is most common among people of Asian descent, in part due to their having a more crowded anterior chamber (2, 3). With a rapid increase in intraocular pressure (IOP) to levels exceeding retinal perfusion pressure, there is resulting retinal ischemia and retinal ganglion cell (RGC) death. Individuals with angle closure glaucoma are much more likely to lose vision and become blind than those with primary open-angle glaucoma (4). The precise mechanisms by which elevated IOP leads to RGC death are not well understood. Accumulating evidence suggests that overactivated microglia have pivotal roles in triggering neurotoxicity in the CNS, including retinal inflammatory responses (5, 6), by producing proinflammatory factors such as IL-1β. IL-1β production is tightly controlled as part of the innate immune response in the CNS (7).Toll-like receptors (TLRs) and Nod-like receptors (NLRs) are two key pattern recognition receptors (PRRs) in the initiation of the innate immune response (8-10). TLR4 has been shown to have a central role in retinal and CNS ischemia/reperfusion (I/R) injuries (11-13). Neuronal death following ischemic injury activates intense inflammation, which triggers TLR4 signaling. It has been demonstrated that ...

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“…TNF‐α played a pivotal role in regulating neuron death caused by retinal I/R injury 47, 48. IL‐1β was involved in the degeneration of inner retinal compositions owe to I/R injury 49. The iNOS‐triggered delayed neuronal cell death after ischaemia mediated the production of nitric oxide (NO),50 which would finally develop into inflammatory oxidants 51.…”

Section: Discussionmentioning

confidence: 99%

Collagen peptide modified carboxymethyl cellulose as both antioxidant drug and carrier for drug delivery against retinal ischaemia/reperfusion injury

Mao

Wang

Wei

et al. 2018

J Cellular Molecular Medi

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Oxidative stress can cause injury in retinal endothelial cells. Carboxymethyl cellulose modified with collagen peptide (CMCC) is of a distinct antioxidant capacity and potentially a good drug carrier. In this study, the protective effects of CMCC against H2O2‐induced injury of primary retinal endothelial cells were investigated. In vitro, we demonstrated that CMCC significantly promoted viability of H2O2‐treated cells, efficiently restrained cellular reactive oxygen species (ROS) production and cell apoptosis. Then, the CMCC was employed as both drug and anti‐inflammatory drug carrier for treatment of retinal ischaemia/reperfusion (I/R) in rats. Animals were treated with CMCC or interleukin‐10‐loaded CMCC (IL‐10@CMCC), respectively. In comparisons, the IL‐10@CMCC treatment exhibited superior therapeutic effects, including better restoration of retinal structural thickness and less retinal apoptosis. Also, chemiluminescence demonstrated that transplantation of IL‐10@CMCC markedly reduced the retinal oxidative stress level compared with CMCC alone and potently recovered the activities of typical antioxidant enzymes, SOD and CAT. Therefore, it could be concluded that CMCC provides a promising platform to enhance the drug‐based therapy for I/R‐related retinal injury.

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Interleukin-1β Mediates Ischemic Injury in the Rat Retina

Cited by 104 publications

References 42 publications

CD40 Mediates Retinal Inflammation and Neurovascular Degeneration

CD40 Mediates Retinal Inflammation and Neurovascular Degeneration

Caspase-8 promotes NLRP1/NLRP3 inflammasome activation and IL-1β production in acute glaucoma

Collagen peptide modified carboxymethyl cellulose as both antioxidant drug and carrier for drug delivery against retinal ischaemia/reperfusion injury

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