Accumulation of murine subretinal macrophages: effects of age, pigmentation and CX3CR1

Chinnery, Holly R.; McLenachan, Samuel; Humphries, Timothy; Kezic, Jelena; Chen, Xiangting; Ruitenberg, Marc J.; McMenamin, Paul G.

doi:10.1016/j.neurobiolaging.2011.03.010

Cited by 69 publications

(63 citation statements)

References 39 publications

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“…29 Additionally, we and others have demonstrated the age-related increase in subretinal macrophage number, which is accelerated in Cx 3 cr1-deficient mice. 32,35 Our study gave us the opportunity to extend these observations using our newly developed ''Green Akita'' mice. Thus, cell densities of Iba-1 þ hyalocytes and subretinal macrophages were calculated on retinal whole mounts and compared between nondiabetic and diabetic groups.…”

Section: Cr1 Deficiency Results In the Accumulation Of Hyalocytementioning

confidence: 91%

“…2B), but not Cx 3 cr1 gfp/þ mice (not shown), indicating these changes were associated with Cx 3 cr1-deficiency as described previously. 32,33 These focal lesions were more pronounced in Cx 3 cr1-deficient Ins2 Akita mice (Fig. 2B), suggesting diabetes may accelerate these retinal changes, and likely are representative of subretinal macrophage accumulation, which is a well documented phenomenon in Cx 3 cr1-deficient mice with aging.…”

Section: Cr1 Deficiency Influences the Development Of Hyperglycementioning

confidence: 82%

“…2B), suggesting diabetes may accelerate these retinal changes, and likely are representative of subretinal macrophage accumulation, which is a well documented phenomenon in Cx 3 cr1-deficient mice with aging. 32,34,35 In vivo fluorescence imaging of the retina at 10 (Fig. 3A), 20, and 30 (see Supplementary Material and Supplementary Fig.…”

Section: Cr1 Deficiency Influences the Development Of Hyperglycementioning

confidence: 99%

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The Effects of Age and Cx₃cr1 Deficiency on Retinal Microglia in theIns2^AkitaDiabetic Mouse

Kezic

Chen

Rakoczy

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Diabetic retinopathy (DR) is a major cause of visual impairment in developed countries. While DR has been described classically as a microvascular disease, recent evidence suggests that changes to retinal microglia are an early feature of retinopathy. In our study, we assessed changes in microglial distribution and morphology in vivo and ex vivo in a mouse model of non-proliferative DR, and further examined effects of age and the absence of the functional chemokine receptor Cx 3 cr1 on the progression of these changes. METHODS.To isolate the effects of the three variables: diabetic status, age, and role of Cx 3 cr1, the Ins2Akita mouse was crossed with Cx 3 cr1-eGFP reporter mice. Eyes were assessed clinically in vivo at 10, 20, 30, and 46 weeks of age, and the retinal structure and arrangement of GFP þ microglia was examined ex vivo using whole mount immunofluorescence staining and confocal microscopy.RESULTS. Clinical examination of the fundus, vasculature, or GFP þ microglial distribution did not reveal any macroscopic changes related to diabetic status: however, ex vivo microscopic analysis revealed alterations in microglial network organization, and evidence of cell shape changes regarded classically as signs of activation, in Ins2Akita mice from 10 weeks of age. These changes were exacerbated in older diabetic mice whose microglia lacked Cx 3 cr1 (Ins2 Akita Cx 3 cr1 gfp/gfp mice). Diabetic status and Cx 3 cr1 deficiency led to accumulations of Iba-1 þ hyalocytes (vitreal macrophages) and subretinal macrophages.CONCLUSIONS. These data showed that changes to murine retinal microglia occur in response to systemic diabetic status in the absence of overt retinopathy and inflammation. These changes are exaggerated in mice lacking Cx 3 cr1, suggesting fractalkineCx 3 cr1 interactions may have a role in early neuronal changes in preproliferative DR. (Invest Ophthalmol Vis Sci.

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Section: Cr1 Deficiency Results In the Accumulation Of Hyalocytementioning

confidence: 91%

Section: Cr1 Deficiency Influences the Development Of Hyperglycementioning

confidence: 82%

Section: Cr1 Deficiency Influences the Development Of Hyperglycementioning

confidence: 99%

See 1 more Smart Citation

The Effects of Age and Cx₃cr1 Deficiency on Retinal Microglia in theIns2^AkitaDiabetic Mouse

Kezic

Chen

Rakoczy

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…The mechanisms of pathogen recognition and initiation of innate defense in this disease are not well understood but are presumed to involve retinal glial cells. Among the potential retinal glial cells involved in antimicrobial defense are microglia, which represent the resident mononuclear phagocyte population present in the central nervous system (CNS) (9). These cells share many phenotypic and functional characteristics with macrophages (60) and are uniquely poised to provide the first line of defense against invading pathogens, even prior to leukocyte infiltration.…”

mentioning

confidence: 99%

Toll-Like Receptor 2 Ligand Pretreatment Attenuates Retinal Microglial Inflammatory Response but Enhances Phagocytic Activity toward Staphylococcus aureus

et al. 2012

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ABSTRACTStaphylococcus aureusis a leading cause of severe endophthalmitis, which often results in vision loss in some patients. Previously, we showed that Toll-like receptor 2 (TLR2) ligand pretreatment prevented the development of staphylococcal endophthalmitis in mice and suggested that microglia might be involved in this protective effect (Kumar A, Singh CN, Glybina IV, Mahmoud TH, Yu FS. J. Infect. Dis. 201:255–263, 2010). The aim of the present study was to understand how microglial innate response is modulated by TLR2 ligand pretreatment. Here, we demonstrate thatS. aureusinfection increased the CD11b+CD45+microglial/macrophage population in the C57BL/6 mouse retina. Using cultured primary retinal microglia and a murine microglial cell line (BV-2), we found that these cells express TLR2 and that its expression is increased upon stimulation with bacteria or an exclusive TLR2 ligand, Pam3Cys. Furthermore, challenge of primary retinal microglia withS. aureusand its cell wall components peptidoglycan (PGN) and lipoteichoic acid (LTA) induced the secretion of proinflammatory mediators (tumor necrosis factor alpha [TNF-α] and MIP-2). This innate response was attenuated by a function-blocking anti-TLR2 antibody or by small interfering RNA (siRNA) knockdown of TLR2. In order to assess the modulation of the innate response, microglia were pretreated with a low dose (0.1 or 1 μg/ml) of Pam3Cys and then challenged with liveS. aureus. Our data showed thatS. aureus-induced production of proinflammatory mediators is dramatically reduced in pretreated microglia. Importantly, microglia pretreated with the TLR2 agonist phagocytosed significantly more bacteria than unstimulated cells. Together, our data suggest that TLR2 plays an important role in retinal microglial innate response toS. aureus, and its sensitization inhibits inflammatory response while enhancing phagocytic activity.

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“…Using human donor eyes from patients with various retinal degenerative diseases like ABCA4-associated Stargardt disease, Best disease and AMD, we have shown that loss of RPE is a common characteristic among these disorders (Mullins et al, , 2007. Support for the BRB playing a major role in conferring protection from the systemic immune system lies in evidence that the subretinal space becomes much more proinflammatory in the face of photoreceptor and RPE degeneration (Chinnery et al, 2012;Mullins et al, 2012;Rutar et al, 2010). There are also reports that inflammation is heavily involved in the pathogenesis of AMD (Ambati et al, 2013;Anand et al, 2003;Tarallo et al, 2012;Whitcup et al, 2013).…”

Section: Retinal Immune Landscapementioning

confidence: 98%

Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases

Wiley

Burnight

Songstad

et al. 2015

Progress in Retinal and Eye Research

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Accumulation of murine subretinal macrophages: effects of age, pigmentation and CX3CR1

Cited by 69 publications

References 39 publications

The Effects of Age and Cx₃cr1 Deficiency on Retinal Microglia in theIns2^AkitaDiabetic Mouse

The Effects of Age and Cx₃cr1 Deficiency on Retinal Microglia in theIns2^AkitaDiabetic Mouse

Toll-Like Receptor 2 Ligand Pretreatment Attenuates Retinal Microglial Inflammatory Response but Enhances Phagocytic Activity toward Staphylococcus aureus

Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases

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Accumulation of murine subretinal macrophages: effects of age, pigmentation and CX3CR1

Cited by 69 publications

References 39 publications

The Effects of Age and Cx3cr1 Deficiency on Retinal Microglia in theIns2AkitaDiabetic Mouse

The Effects of Age and Cx3cr1 Deficiency on Retinal Microglia in theIns2AkitaDiabetic Mouse

Toll-Like Receptor 2 Ligand Pretreatment Attenuates Retinal Microglial Inflammatory Response but Enhances Phagocytic Activity toward Staphylococcus aureus

Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases

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Product

Resources

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The Effects of Age and Cx₃cr1 Deficiency on Retinal Microglia in theIns2^AkitaDiabetic Mouse

The Effects of Age and Cx₃cr1 Deficiency on Retinal Microglia in theIns2^AkitaDiabetic Mouse