Proliferation of Microglia, but not Photoreceptors, in the Outer Nuclear Layer of the<i>rd-1</i>Mouse

Zeiss, Caroline J.; Johnson, Elizabeth A.

doi:10.1167/iovs.03-0301

Cited by 103 publications

(96 citation statements)

References 37 publications

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“…It has been shown recently that microglial migration and accumulation is enhanced in the degenerating retina such as in that of the RCS rat (Roque et al 1996), the rd1 (Zeiss and Johnson 2004;Andrieu-Soler et al 2005;Zeng et al 2005) or the rd2 mouse (Hughes et al 2003). Zeng and coworkers (Zeng et al 2005) have additionally shown in the rd1 retina that activated microglia express a multitude of signaling molecules (chemokines MCP-1, MCP-3, MIP-1α , MIP-1β, and RANTES) and microglia-derived toxic factor (TNF-α ) which may contribute to three different processes: 1 st , increased photoreceptor death due to the release of cytotoxic substances; 2 nd , recruitment of monocytes/macrophages to the site of injury through the release of chemokines and 3 rd , removal of cellular debris.…”

Section: Discussionmentioning

confidence: 99%

Classical complement activation and acquired immune response pathways are not essential for retinal degeneration in the rd1 mouse

Rohrer

Demos

Frigg

et al. 2007

Experimental Eye Research

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Misregulation of the innate immune response and other immune-related processes have been suggested to play a critical role in the pathogenesis of a number of different neurodegenerative diseases, including age related macular degeneration. In an animal model for photoreceptor degeneration, several genes of the innate and acquired immune system were found to be differentially regulated in the retina during the degenerative process. In addition to this differential regulation of individual genes, we found that in the rd1 retina a significantly higher number of genes involved in immune-related responses were expressed at any given time during the degenerative period. The peak of immune-related gene expression was at postnatal day 14, coinciding with the peak of photoreceptor apoptosis in the rd1 mouse. We directly tested the potential involvement of acquired and innate immune responses in initiation and progression of photoreceptor degeneration by analyzing double mutant animals. Retinal morphology and photoreceptor apoptosis of rd1 mice on a SCID genetic background (no mature T-and B-cells) or in combination with a RAG-1 (no functional B-and T-cells) or a C1qα (no functional classical complement activation pathway) knockout was followed during the degenerative process using light microscopy or TUNEL staining, respectively. Although complement factor C1qα was highly up-regulated in the rd1 retina concomitantly with the degenerative process, lack of this protein did not protect the rd1 retina. Similarly, retinal degeneration and photoreceptor apoptosis appeared to proceed normally in the rd1 mouse lacking functional Band T-cells. Our results suggest that both, the classical complement system of innate immunity and a functional acquired immune response are not essential for the degenerative process in the rd1 mouse retina.

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Section: Discussionmentioning

confidence: 99%

Classical complement activation and acquired immune response pathways are not essential for retinal degeneration in the rd1 mouse

Rohrer

Demos

Frigg

et al. 2007

Experimental Eye Research

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“…Similar results have been described in the rd-1 mouse, in which a population of proliferating cells in the ONL accompanies photoreceptor death. These dividing cells have been identified as microglial cells originating from the inner retina (Zeiss and Johnson, 2004). However, other studies have not detected microglial proliferation in experimentally induced neurodegeneration in mammals (Rogove et al, 2002;Santos et al, 2010).…”

Section: Microglia In the Experimental Tench Retinal Tissuementioning

confidence: 99%

“…Furthermore, retinal microglia are activated in response to nearly all pathological stages of the retina (Langmann, 2007), with microglial cells migrating to the layers affected by degeneration. Thus, the adult ONL which is normally devoid of microglial cells Santos et al, 2008;Bejarano-Escobar et al, 2011), is colonized by these cells in conditions of photoreceptor degeneration during normal development (Bejarano-Escobar et al, 2011) or under pathological or experimental conditions (Roque et al, 1996;Ng and Streilein, 2001;Harada et al, 2002;Hughes et al, 2003;Zeiss and Johnson, 2004;Zeng et al, 2005;Bailey et al, 2010;Santos et al, 2010).…”

Section: Microglia In the Experimental Tench Retinal Tissuementioning

confidence: 99%

Light-induced degeneration and microglial response in the retina of an epibenthonic pigmented teleost: age-dependent photoreceptor susceptibility to cell death

Bejarano-Escobar

Blasco²,

Martı́n-Partido

et al. 2012

Journal of Experimental Biology

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SUMMARYConstant intense light causes apoptosis of photoreceptors in the retina of albino fish. However, very few studies have been performed on pigmented species. Tench (Tinca tinca) is a teleost inhabiting dimly lit environments that has a predominance of rods within the photoreceptor layer. To test the hypothesis that constant high intensity light can result in retinal damage in such pigmented epibenthonic teleost species, photodegeneration of the retina was investigated in the larvae and in juveniles of tench to assess whether any damage may also be dependent on fish age. We exposed both groups of animals to 5days of constant darkness, followed by 4days of constant 20,000lx light, and then by 6days of recovery in a 14h light:10h dark cycle. The results showed that the retina of the larvae group exhibited abundant photoreceptor cell apoptosis during the time of exposition to intense light, whereas that of juveniles was indifferent to it. Damaged retinas showed a strong TUNEL signal in photoreceptor nuclei, and occasionally a weak cytoplasmic TUNEL signal in Müller glia. Specific labelling of microglial cells with Griffonia simplicifolia lectin (GSL) histochemistry revealed that photoreceptor cell death alerts microglia in the degenerating retina, leading to local proliferation, migration towards the injured outer nuclear layer (ONL), and enhanced phagocytosis of photoreceptor debris. During the first days of intense light treatment, Müller cells phagocytosed dead photoreceptor cells but, once microglial cells became activated, there was a progressive increase in the phagocytic capacity of the microglia.

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“…However, excessive or prolonged microglial activation in the CNS and the retina can lead to chronic inflammation with severe pathological side effects often resulting in irreversible neuronal loss (2,20,21). In eye research, various animal models have demonstrated that microglial activation is tightly associated with and mostly precedes retinal degeneration and photoreceptor apoptosis (22)(23)(24). Functional and phenotypic characterization of microglia populations in the diseased retina could be of high relevance to reveal signaling events that trigger their activation.…”

mentioning

confidence: 99%

The Novel Activated Microglia/Macrophage WAP Domain Protein, AMWAP, Acts as a Counter-Regulator of Proinflammatory Response

Karlstetter

Walczak

Weigelt

et al. 2010

The Journal of Immunology

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Proliferation of Microglia, but not Photoreceptors, in the Outer Nuclear Layer of therd-1Mouse

Cited by 103 publications

References 37 publications

Classical complement activation and acquired immune response pathways are not essential for retinal degeneration in the rd1 mouse

Classical complement activation and acquired immune response pathways are not essential for retinal degeneration in the rd1 mouse

Light-induced degeneration and microglial response in the retina of an epibenthonic pigmented teleost: age-dependent photoreceptor susceptibility to cell death

The Novel Activated Microglia/Macrophage WAP Domain Protein, AMWAP, Acts as a Counter-Regulator of Proinflammatory Response

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