Blood-derived macrophages infiltrate the retina and activate Muller glial cells under experimental choroidal neovascularization

Caicedo, Alejandro; Espinosa‐Heidmann, Diego G.; Piña, Yolanda; Hernandez, E.; Cousins, Scott W.

doi:10.1016/j.exer.2005.01.013

Cited by 144 publications

(117 citation statements)

References 46 publications

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“…Laser coagulation of the mouse choroid induces a local inflammatory reaction composed of blood-derived macrophages and activated MCs (25). After detecting SrMC accumulation in senescent and ambient light-exposed CX3CR1-deficient mice, we studied the influence of CX3CR1 deficiency in laser injury.…”

Section: Drusen Observed In Cx3cr1 Knockout Mice Are Lipid-bloated Srmentioning

confidence: 99%

CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration

Combadière¹,

Feumi²,

Raoul³

et al. 2007

J. Clin. Invest.

512

653

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The role of retinal microglial cells (MCs) in age-related macular degeneration (AMD) is unclear. Here we demonstrated that all retinal MCs express CX3C chemokine receptor 1 (CX3CR1) and that homozygosity for the CX3CR1 M280 allele, which is associated with impaired cell migration, increases the risk of AMD. In humans with AMD, MCs accumulated in the subretinal space at sites of retinal degeneration and choroidal neovascularization (CNV). In CX3CR1-deficient mice, MCs accumulated subretinally with age and albino background and after laser impact preceding retinal degeneration. Raising the albino mice in the dark prevented both events. The appearance of lipid-bloated subretinal MCs was drusen-like on funduscopy of senescent mice, and CX3CR1-dependent MC accumulation was associated with an exacerbation of experimental CNV. These results show that CX3CR1-dependent accumulation of subretinal MCs evokes cardinal features of AMD. These findings reveal what we believe to be a novel pathogenic process with important implications for the development of new therapies for AMD.

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Section: Drusen Observed In Cx3cr1 Knockout Mice Are Lipid-bloated Srmentioning

confidence: 99%

CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration

Combadière¹,

Feumi²,

Raoul³

et al. 2007

J. Clin. Invest.

512

653

View full text Add to dashboard Cite

show abstract

“…As such, perturbation of expression of ligand or receptor during stress would activate microglia to produce proinflammatory cytokines and acquire an activated morphology (11,64). Activated microglia produce chemokines such as monocyte chemoattractant protein-1 (11), inducing expression of adhesion molecules, which can promote the leukostasis of neutrophils, on endothelium (65) and potentially inducing the extravasation of inflammatory macrophages (66). In addition, elevated levels of complement and reduced levels of complement inhibitors (67) and acute-phase proteins (68) are likely key events in the phagocytic clearance of necrotic and apoptotic neurons (12).…”

Section: Fig 2 Functional Anatomy Of the Retina Metabolic Interactmentioning

confidence: 99%

Diabetic Retinopathy

et al. 2006

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Diabetic retinopathy remains a frightening prospect to patients and frustrates physicians. Destruction of damaged retina by photocoagulation remains the primary treatment nearly 50 years after its introduction. The diabetes pandemic requires new approaches to understand the pathophysiology and improve the detection, prevention, and treatment of retinopathy. This perspective considers how the unique anatomy and physiology of the retina may predispose it to the metabolic stresses of diabetes. The roles of neural retinal alterations and impaired retinal insulin action in the pathogenesis of early retinopathy and the mechanisms of vision loss are emphasized. Potential means to overcome limitations of current animal models and diagnostic testing are also presented with the goal of accelerating therapies to manage retinopathy in the face of ongoing diabetes. Diabetes 55:2401-2411, 2006 D espite years of clinical and laboratory investigation, diabetic retinopathy remains the leading cause of vision impairment and blindness among working-age adults, yet the fundamental cause(s) remains uncertain. Retinal photocoagulation to reduce neovascularization and macular edema was developed in the 1950s and is still the standard of care (1). The number of people worldwide at risk of developing vision loss from diabetes is predicted to double over the next 30 years (2), so it is imperative to develop better means to identify, prevent, and treat retinopathy in its earliest stages rather than wait for the onset of vision-threatening lesions. Progress in these areas requires a new perspective on the problem that includes the roles of the neural retina, impaired insulin action, and inflammation. In this way, established neurobiological principles can inform us how diabetes impairs vision, and knowledge of metabolism, inflammation, and regenerative medicine may lead to new treatments.This perspective will discuss how the unique anatomy and physiology of the retina may render it vulnerable to the metabolic derangements of diabetes and lead to impaired vision. The intent of this unconventional approach is to encourage consideration of new opportunities for investigations that will advance the field. NORMAL RETINAL STRUCTURE AND PHYSIOLOGY Topographic and cellular organization of the retina.It is instructive to consider the functional organization of the retina (literally a network) to better understand the impact of diabetes (http://webvision.med.utah.edu). The retina is a transparent layer of neural tissue between the retinal pigmented epithelium and the vitreous body. Normal vision depends on intact cell-cell communication among the neuronal, glial, microglial, vascular, and pigmented epithelial cells of the retina. The fundamental functions of the retina are to capture photons, convert the photochemical energy into electrical energy, integrate the resulting action potentials, and transmit them to the occipital lobe of the brain, where they are deciphered and interpreted into recognizable images. The retina is partitioned from the syst...

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“…29 A special subset of blood monocytes is destined as microglia precursor cell. 30 Recruitment of bone marrow-derived cells into the retina has been observed after different stimuli including retinal lesions [31][32][33] and inherited retinal degeneration.…”

Section: Bone Marrow Chimeric Micementioning

confidence: 99%

Cooperative Phagocytes

Joly

Francke

Ulbricht

et al. 2009

The American Journal of Pathology

132

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Phagocytosis is essential for the removal of photoreceptor debris following retinal injury. We used two mouse models, mice injected with green fluorescent protein-labeled bone marrow cells or green fluorescent protein-labeled microglia, to study the origin and activation patterns of phagocytic cells after acute blue light-induced retinal lesions. We show that following injury, blood-borne macrophages enter the eye via the optic nerve and ciliary body and soon migrate into the injured retinal area. Resident microglia are also activated rapidly throughout the entire retina and adopt macrophage characteristics only in the injured region. Both blood-borne-and microgliaderived macrophages were involved in the phagocytosis of dead photoreceptors. No obvious breakdown of the blood-retinal barrier was observed. Ccl4, Ccl12, Tgfb1, Csf1, and Tnf were differentially expressed in both the isolated retina and the eyecup of wild-type mice. Debris-laden macrophages appeared to leave the retina into the general circulation, suggesting their potential to become antigen-presenting cells. These experiments provide evidence that both local and immigrant macrophages remove apoptotic photoreceptors and cell debris in the injured retina.

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Blood-derived macrophages infiltrate the retina and activate Muller glial cells under experimental choroidal neovascularization

Cited by 144 publications

References 46 publications

CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration

CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration

Diabetic Retinopathy

Cooperative Phagocytes

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