Expression of Complement Component 3 (C3) from an Adenovirus Leads to Pathology in the Murine Retina

Cashman, Siobhan M.; Desai, Akshata; Ramo, Kasmir; Kumar‐Singh, Rajendra

doi:10.1167/iovs.10-6002

Cited by 45 publications

(37 citation statements)

References 59 publications

(60 reference statements)

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“…Dysregulation of C3 plays a highly significant role in retinal diseases, and dysregulation of complement is highly associated with risk of AMD [49,50,52]. Several lines of evidence suggest that oxidative stress triggers complement activation [53,54], which in turn mediates local inflammation.…”

Section: Discussionmentioning

confidence: 99%

670 nm light mitigates oxygen-induced degeneration in C57BL/6J mouse retina

Albarracin¹,

Natoli

Rutar³

et al. 2013

BMC Neurosci

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BackgroundIrradiation with light wavelengths from the far red (FR) to the near infrared (NIR) spectrum (600 nm -1000 nm) has been shown to have beneficial effects in several disease models. In this study, we aim to examine whether 670 nm red light pretreatment can provide protection against hyperoxia-induced damage in the C57BL/6J mouse retina. Adult mice (90–110 days) were pretreated with 9 J/cm2 of 670 nm light once daily for 5 consecutive days prior to being placed in hyperoxic environment (75% oxygen). Control groups were exposed to hyperoxia, but received no 670 nm light pretreatment. Retinas were collected after 0, 3, 7, 10 or 14 days of hyperoxia exposure (n = 12/group) and prepared either for histological analysis, or RNA extraction and quantitative polymerase chain reaction (qPCR). Photoreceptor damage and loss were quantified by counting photoreceptors undergoing cell death and measuring photoreceptor layer thickness. Localization of acrolein, and cytochrome c oxidase subunit Va (Cox Va) were identified through immunohistochemistry. Expression of heme oxygenase-1 (Hmox-1), complement component 3 (C3) and fibroblast growth factor 2 (Fgf-2) genes were quantified using qPCR.ResultsThe hyperoxia-induced photoreceptor loss was accompanied by reduction of metabolic marker, Cox Va, and increased expression of oxidative stress indicator, acrolein and Hmox-1. Pretreatment with 670 nm red light reduced expression of markers of oxidative stress and C3, and slowed, but did not prevent, photoreceptor loss over the time course of hyperoxia exposure.ConclusionThe damaging effects of hyperoxia on photoreceptors were ameliorated following pretreatment with 670 nm light in hyperoxic mouse retinas. These results suggest that pretreatment with 670 nm light may provide stability to photoreceptors in conditions of oxidative stress.

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Section: Discussionmentioning

confidence: 99%

670 nm light mitigates oxygen-induced degeneration in C57BL/6J mouse retina

Albarracin¹,

Natoli

Rutar³

et al. 2013

BMC Neurosci

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“…Indeed, mice eyes develop many features of AMD when exposed to C3 administered via an adenovirus vector delivered by subretinal injection (Cashman et al 2011a). C3 and its activation product C3a have been found in drusen, as well as in neuroretina, BM and choroidal stroma (Mullins et al 2001;Nozaki et al 2006;Gold et al 2006).…”

Section: Complement C3mentioning

confidence: 99%

Age-related macular degeneration and the complement system

et al. 2012

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“…In particular, exogenous expression of C3 induces both blood vessel leakiness and endothelial cell proliferation in the murine retina. Finally, the C3-injected eyes displayed significantly reduced cone and rod function as measured by ERG, and this reduction was consistent with the loss of photoreceptor segments [85]. …”

Section: The Detrimental Role Of the Complement System In Retinal mentioning

confidence: 66%

“…In addition, Nozaki et al found that C3a and C5a induce VEGF expression in the mouse RPE in vitro and in vivo and thus may accelerate the model of neovascular AMD [82]. Similarly, Cashman et al observed that the conditionally increased expression of C3 in RPE obtained by intraocular injection of an adenovirus-expressing murine C3 caused significant functional and anatomic changes in the retina, which reproduce many of the features characteristic of AMD and other retinal diseases [85]. In particular, exogenous expression of C3 induces both blood vessel leakiness and endothelial cell proliferation in the murine retina.…”

Section: The Detrimental Role Of the Complement System In Retinal mentioning

confidence: 99%

Complement System in Pathogenesis of AMD: Dual Player in Degeneration and Protection of Retinal Tissue

Kawa

Machalińska

Rogińska

et al. 2014

Journal of Immunology Research

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Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly, especially in Western countries. Although the prevalence, risk factors, and clinical course of the disease are well described, its pathogenesis is not entirely elucidated. AMD is associated with a variety of biochemical abnormalities, including complement components deposition in the retinal pigment epithelium-Bruch's membrane-choriocapillaris complex. Although the complement system (CS) is increasingly recognized as mediating important roles in retinal biology, its particular role in AMD pathogenesis has not been precisely defined. Unrestricted activation of the CS following injury may directly damage retinal tissue and recruit immune cells to the vicinity of active complement cascades, therefore detrimentally causing bystander damage to surrounding cells and tissues. On the other hand, recent evidence supports the notion that an active complement pathway is a necessity for the normal maintenance of the neurosensory retina. In this scenario, complement activation appears to have beneficial effect as it promotes cell survival and tissue remodeling by facilitating the rapid removal of dying cells and resulting cellular debris, thus demonstrating anti-inflammatory and neuroprotective activities. In this review, we discuss both the beneficial and detrimental roles of CS in degenerative retina, focusing on the diverse aspects of CS functions that may promote or inhibit macular disease.

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Expression of Complement Component 3 (C3) from an Adenovirus Leads to Pathology in the Murine Retina

Cited by 45 publications

References 59 publications

670 nm light mitigates oxygen-induced degeneration in C57BL/6J mouse retina

670 nm light mitigates oxygen-induced degeneration in C57BL/6J mouse retina

Age-related macular degeneration and the complement system

Complement System in Pathogenesis of AMD: Dual Player in Degeneration and Protection of Retinal Tissue

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