Peroxynitrite-induced apoptosis in photoreceptor cells

Ito, Shinji; Wu, Guey-Shuang; Kimoto, Takashi; Hisatomi, Toshio; Ishibashi, Tatsuro; Rao, Narsing A.

doi:10.1076/ceyr.28.1.17.23488

Cited by 15 publications

(12 citation statements)

References 13 publications

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“…We also showed that in EAU, mitochondrial oxidative stress occurs before macrophage or other inflammatory cellular infiltration [7]. These findings support previous studies from our laboratory that determined that peroxynitrite-mediated nitration of photoreceptor mitochondrial proteins, as well as the presence of reactive oxidants and peroxynitrite, occurs in mitochondrial photoreceptors during early EAU [17, 18]. Oxidative stress appears to target the mitochondria as the original site of inflammation and thus damaged or altered mtDNA is a major target for oxidative damage.…”

Section: Photoreceptor Mitochondrial Oxidative Stresssupporting

confidence: 89%

“…Prior to leukocyte infiltration during early EAU, selective peroxynitrite-mediated nitration of photoreceptor mitochondrial proteins occurs [17]. Our studies show that in the early stages of EAU, mitochondria are the major source of ONOO − , and mitochondrial proteins are the prime target for inactivation, further implicating photoreceptor mitochondria as initiators of the proinflammatory response in early EAU [6].…”

Section: Introductionmentioning

confidence: 91%

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Oxidative photoreceptor cell damage in autoimmune uveitis

Nguyen

Rao

2010

J Ophthal Inflamm Infect

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Uveitis comprises an extensive array of intraocular inflammatory diseases and often results in irreversible visual loss. Experimental autoimmune uveitis (EAU) is an animal model used to study human uveitis. Both innate and adaptive immune responses are known to mediate retinal damage in EAU. The innate immune response occurs first with activation of toll-like receptors which upregulate inflammatory cytokines, leading to oxidative stress; subsequently, the adaptive immune response results in inflammatory cytokine upregulation and mitochondrial oxidative stress. In early EAU, mitochondrial DNA is damaged before inflammatory cellular infiltration and alters mitochondrial protein levels and the functions of mitochondria in AU. Our recent study confirms the importance of TLR4 in the generation of inflammatory cytokines, initiation of oxidative DNA damage, and induction of mitochondrial oxidative stress. Like EAU, sympathetic ophthalmia also results in photoreceptor mitochondrial oxidative damage. Agents that prevent mitochondrial oxidative stress and photoreceptor apoptosis may help prevent retinal damage and preserve vision in uveitis.

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Section: Photoreceptor Mitochondrial Oxidative Stresssupporting

confidence: 89%

Section: Introductionmentioning

confidence: 91%

Oxidative photoreceptor cell damage in autoimmune uveitis

Nguyen

Rao

2010

J Ophthal Inflamm Infect

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“…We further evaluated the protective effect of propofol on peroxynitrite mediated apoptosis as it occurs in photoreceptors cells (Ito, S., 2004) and in cerebral vascular muscle cells (Li, J., 2003). Traditionally, necrosis was believed to be the predominant mechanism of astrocyte death in CNS injury models.…”

Section: Discussionmentioning

confidence: 99%

Propofol Inhibits Caspase-3 in Astroglial Cells: Role of Heme Oxygenase-1

Acquaviva¹,

Campisi²,

Raciti³

et al. 2005

CNR

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Several lines of evidence have extensively demonstrated that peroxynitrite plays a pivotal role in Central Nervous System (CNS) injuries. The present study was aimed at elucidating the molecular mechanism by which propofol attenuates peroxynitrite-mediated injury in the brain. Primary cultured astroglial cells were incubated for 18 h with a known peroxynitrite donor (SIN-1,3 mM) in the presence or absence of propofol (40 microM, 80 microM and 160 microM). The protective effects of propofol were evaluated by MTT cytotoxicity assay, LDH release, and caspase-3 activation by Western blot analysis. Appropriate propofol concentrations (ranging from 40 microM to 160 microM) significantly increased HO-1 expression and attenuated SIN-1-mediated cytotoxicity and caspase-3 activation. The protective effects of propofol were mitigated by the addition of tin-mesoporphirin (SnMP), a potent inhibitor of HO activity. The addition of a specific synthetic inhibitor of NF-kappaB abolished propofol-mediated HO-1 induction, suggesting a possible role for this nuclear transcriptional factor in our experimental conditions. These findings indicate that propofol attenuates peroxynitrite-mediated apoptosis in astroglial cells, a property that may be relevant in both physiological and pathological processes in the CNS.

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“…Macrophages and T cells typically infiltrate the retina in the early stages of EAU (days 11-12 after immunization). However, in day 5 after immunization, studies have shown peroxynitrite-mediated nitration of photoreceptor mitochondrial proteins [16], leading to mitochondria dysregulation and cell death [17]. Lipofuscins are thought to represent the breakdown product of various retinal proteins as a result of oxidative damage which is thought to play a role in uveitic diseases [18].…”

Section: Introductionmentioning

confidence: 99%

Role of Autofluorescence in Inflammatory/Infective Diseases of the Retina and Choroid

Samy

Lightman

Ismetova

et al. 2014

Journal of Ophthalmology

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Fundus autofluorescence (FAF) has recently emerged as a novel noninvasive imaging technique that uses the fluorescent properties of innate fluorophores accumulated in the retinal pigment epithelium (RPE) to assess the health and viability of the RPE/photoreceptor complex. Recent case reports suggest FAF as a promising tool for monitoring eyes with posterior uveitis helping to predict final visual outcome. In this paper we review the published literature on FAF in these disorders, specifically patterns in infectious and noninfectious uveitis, and illustrate some of these with short case histories.

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Peroxynitrite-induced apoptosis in photoreceptor cells

Abstract: These results show that peroxynitrite induces apoptosis in photoreceptor cells and that such retinal damage appears to be mediated by caspase-3. The apoptotic process can be minimized by peroxynitrite scavenger urate, as well as by the caspase inhibitor Z-VAD-fmk.

Cited by 15 publications

References 13 publications

Oxidative photoreceptor cell damage in autoimmune uveitis

Oxidative photoreceptor cell damage in autoimmune uveitis

Propofol Inhibits Caspase-3 in Astroglial Cells: Role of Heme Oxygenase-1

Role of Autofluorescence in Inflammatory/Infective Diseases of the Retina and Choroid

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