Generation of Activated Sialoadhesin-Positive Microglia during Retinal Degeneration

Hughes, Edward; Schlichtenbrede, Frank C.; Murphy, Conor C; Sarra, Gian-Marco; Luthert, Philip J.; Ali, Robin R.; Dick, Andrew D.

doi:10.1167/iovs.02-0824

Cited by 73 publications

(61 citation statements)

References 27 publications

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“…Moreover, infiltrating macrophages are thought to participate in the inflammation associated with retinal degeneration (56)(57)(58). Retinal macrophages Fig.…”

Section: Discussionmentioning

confidence: 99%

Two-photon microscopy reveals early rod photoreceptor cell damage in light-exposed mutant mice

Maeda

Palczewska

Golczak³

et al. 2014

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

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Atrophic age-related and juvenile macular degeneration are especially devastating due to lack of an effective cure. Two retinal cell types, photoreceptor cells and the adjacent retinal pigmented epithelium (RPE), reportedly display the earliest pathological changes. Abca4 −/− Rdh8 −/− mice, which mimic many features of human retinal degeneration, allowed us to determine the sequence of light-induced events leading to retinal degeneration. Using two-photon microscopy with 3D reconstruction methodology, we observed an initial strong retinoid-derived fluorescence and expansion of Abca4 −/− Rdh8 −/− mouse rod cell outer segments accompanied by macrophage infiltration after brief exposure of the retina to bright light. Additionally, light-dependent fluorescent compounds produced in rod outer segments were not transferred to the RPE of mice genetically defective in RPE phagocytosis. Collectively, these findings suggest that for light-induced retinopathies in mice, rod photoreceptors are the primary site of toxic retinoid accumulation and degeneration, followed by secondary changes in the RPE.

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“…Moreover, infiltrating macrophages are thought to participate in the inflammation associated with retinal degeneration (56)(57)(58). Retinal macrophages Fig.…”

Section: Discussionmentioning

confidence: 99%

Two-photon microscopy reveals early rod photoreceptor cell damage in light-exposed mutant mice

Maeda

Palczewska

Golczak³

et al. 2014

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

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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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“…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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Generation of Activated Sialoadhesin-Positive Microglia during Retinal Degeneration

Cited by 73 publications

References 27 publications

Two-photon microscopy reveals early rod photoreceptor cell damage in light-exposed mutant mice

Two-photon microscopy reveals early rod photoreceptor cell damage in light-exposed mutant mice

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

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