Scavenger Function of Resident Autofluorescent Perivascular Macrophages and Their Contribution to the Maintenance of the Blood–Retinal Barrier

Mendes-Jorge, Luísa; Ramos, David; Luppo, Mariana; Llombart, Cristina; Alexandre‐Pires, Graça; Nacher, Víctor; Melgarejo, Verònica; Correia, Miguel; Navarro, Marc; Carretero, Ana; Tafuro, Sabrina; Rodríguez‐Baeza, Alfonso; Esperança-Pina, J. A.; Bosch, Fátima; Ruberte, Jesús

doi:10.1167/iovs.09-3515

Cited by 76 publications

(69 citation statements)

References 26 publications

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“…In our study, apoptotic RGCs were observed in 20-week-old db/db mice, consistent with the reduced PERG amplitudes. Moreover, the number of apoptotic cells was increasing with age, accompanied with evident induction of IBA-1 and F4/80 expression, both of which were considered as established marker for microglia/macrophages in the retina [48]. Additionally, IBA-1 and F4/80 positive cells as well as apoptosis cells were also found in the INL, which was implied to be affected by db/db mice.…”

Section: Discussionmentioning

confidence: 99%

Retinal Neurodegeneration in db/db Mice at the Early Period of Diabetes

Yang

Xie

et al. 2015

Journal of Ophthalmology

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Purpose. To describe both the functional and pathological alternations in neurosensory retina in a murine model of spontaneous type 2 diabetes (db/db mouse). Methods. db/db (BKS/DB−/−) mice and heterozygous littermates (as control group) at various ages (12, 16, 20, 24, and 28 weeks) were inspected with pattern electroretinogram (PERG), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). Histological markers of neuroinflammation (IBA-1 and F4/80) were evaluated by immunohistochemistry. In addition, levels of retinal ganglion cell death were measured by terminal dUTP nick-end labeling (TUNEL). Results. Significant alternations of PERG responses and increased retinal ganglion cells (RGCs) apoptosis were observed in diabetic db/db mice for 20-week period when compared with control group. IBA-1 and F4/80 expression in microglia/macrophages became evidently for 24-week period, thus supporting the PERG findings. Furthermore, obvious thinning of nasal and dorsal retina in 28-week-old db/db mice was also revealed by OCT. No visible retinal microvascular changes were detected by FFA throughout the experiments on db/db mice. Conclusions. Diabetic retina underwent neurodegenerative changes in db/db mice, which happened at retinal ganglion cell layer and inner nuclear layer. But there was no obvious abnormality in retinal vasculature on db/db mice.

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Section: Discussionmentioning

confidence: 99%

Retinal Neurodegeneration in db/db Mice at the Early Period of Diabetes

Yang

Xie

et al. 2015

Journal of Ophthalmology

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“…For example, in the area postrema, a circumventricular organ devoid of BBB, PVM restrict the entry of tracers larger than 10 kDa [45]. In addition, in the mouse retina, PVM move along retinal blood vessels and accumulate blood-borne molecules without disruption of the blood-retina barrier [46]. In experimental and human retinopathy, in which the barrier is disrupted, PVM migrate to the lesion site and may play a role in limiting the leakage of blood components into the retina [46].…”

Section: Pathophysiological Role Of Perivascular Macrophagesmentioning

confidence: 99%

Brain perivascular macrophages: characterization and functional roles in health and disease

et al. 2017

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Perivascular macrophages (PVM) are a distinct population of resident brain macrophages characterized by a close association with the cerebral vasculature. PVM migrate from the yolk sac into the brain early in development and, like microglia, are likely to be a self-renewing cell population that, in the normal state, is not replenished by circulating monocytes. Increasing evidence implicates PVM in several disease processes, ranging from brain infections and immune activation to regulation of the hypothalamic-adrenal axis and neurovascular-neurocognitive dysfunction in the setting of hypertension, Alzheimer disease pathology, or obesity. These effects involve crosstalk between PVM and cerebral endothelial cells, interaction with circulating immune cells, and/or production of reactive oxygen species. Overall, the available evidence supports the idea that PVM are a key component of the brain-resident immune system with broad implications for the pathogenesis of major brain diseases. A better understanding of the biology and pathobiology of PVM may lead to new insights and therapeutic strategies for a wide variety of brain diseases.

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“…Several Scara5 positive cells were found within the outer nuclear layer (Figure 8C). The immunolabeling with anti-2F8 antibody, a macrophage marker [44], revealed the presence of 2F8 positive cells also within the outer nuclear layer, suggesting that the Scara5 positive cells observed may correspond to 2F8 positive macrophages that migrated to lesion sites [27].…”

Section: Resultsmentioning

confidence: 90%

“…We received human eye samples without knowledge of the donor's identity, only biological data, such as sex and age, were available. Results obtained from the same human retinas were previously published [27], [28].…”

Section: Methodsmentioning

confidence: 89%

L-Ferritin Binding to Scara5: A New Iron Traffic Pathway Potentially Implicated in Retinopathy

et al. 2014

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Iron is essential in the retina because the heme-containing enzyme guanylate cyclase modulates phototransduction in rods and cones. Transferrin endocytosis is the classical pathway for obtaining iron from the blood circulation in the retina. However, the iron storage protein ferritin has been also recently proposed as an iron carrier. In this study, the presence of Scara5 and its binding to L-ferritin was investigated in the retina. Our results showed that Scara5, the specific receptor for L-ferritin, was expressed in mouse and human retinas in many cell types, including endothelial cells. Furthermore, we showed that intravenously injected ferritin crossed the blood retinal barrier through L-ferritin binding to Scara5 in endothelial cells. Thus, suggesting the existence of a new pathway for iron delivery and trafficking in the retina. In a murine model of photoreceptor degeneration, Scara5 was downregulated, pointing out this receptor as a potential player implicated in retinopathy and also as a possible therapeutic target.

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Scavenger Function of Resident Autofluorescent Perivascular Macrophages and Their Contribution to the Maintenance of the Blood–Retinal Barrier

Cited by 76 publications

References 26 publications

Retinal Neurodegeneration in db/db Mice at the Early Period of Diabetes

Retinal Neurodegeneration in db/db Mice at the Early Period of Diabetes

Brain perivascular macrophages: characterization and functional roles in health and disease

L-Ferritin Binding to Scara5: A New Iron Traffic Pathway Potentially Implicated in Retinopathy

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