New insights into mononuclear phagocyte biology from the visual system

Reyes, Nancy; O’Koren, Emily G.; Saban, Daniel R.

doi:10.1038/nri.2017.13

Cited by 66 publications

(44 citation statements)

References 136 publications

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“…However, we cannot exclude additional retinal cell dysfunction in MPS-IIIA mice that might be due to secondary storage materials and lysosomal impairment effects. Interestingly, previous studies have shown microglia activation associated to retinal dystrophy in mouse models of MPS (Karlstetter et al, 2015;Tse et al, 2015;Kruszewski et al, 2016;Reyes et al, 2017). Therefore, we asked whether the microglia was activated in the retina of MPS-IIIA mice.…”

Section: Photoreceptor Degeneration Is Associated With Inflammation Amentioning

confidence: 94%

Retinal Degeneration in MPS-IIIA Mouse Model

Intartaglia¹,

Giamundo²,

Marrocco³

et al. 2020

Front. Cell Dev. Biol.

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Mucopolysaccharidosis type IIIA (MPS-IIIA, Sanfilippo A) is one of the most severe lysosomal storage disorder (LSD) caused by the inherited deficiency of sulfamidase, a lysosomal sulfatase enzyme involved in the stepwise degradation of heparan sulfates (HS). MPS-IIIA patients show multisystemic problems, including a strong impairment of central nervous system (CNS), mild somatic involvement, and ocular manifestations that result in significant visual impairment. Despite the CNS and somatic pathology have been well characterized, studies on visual system and function remain partially explored. Here, we characterized the retina morphology and functionality in MPS-IIIA mouse model and analyzed how the SGSH deficiency affects the autophagic flux. MPS-IIIA mice exhibited a progressive retinal dystrophy characterized by significant alterations in visual function. The photoreceptor degeneration was associated with HS accumulation and a block of autophagy pathway. These events caused a reactive microgliosis, and a development of apoptotic processes in MPS-IIIA mouse retina. Overall, this study provides the first phenotypic spectrum of retinal disorders in MPS-IIIA and significantly contributes for diagnosis, counseling, and potential therapies development.

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Section: Photoreceptor Degeneration Is Associated With Inflammation Amentioning

confidence: 94%

Retinal Degeneration in MPS-IIIA Mouse Model

Intartaglia¹,

Giamundo²,

Marrocco³

et al. 2020

Front. Cell Dev. Biol.

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“…O'Koren et al () demonstrated that retinal microglia have a unique CD45(low) CD11c(low) F4/80(low) I‐A/I‐E(−) signature which is conserved in the steady state and during retinal injury. By investigating these cells, the authors found that microglia migrate to the photoreceptor outer segments while monocyte‐derived macrophages appear throughout the entire retina (Reyes et al, ). For further insights into microglia heterogeneity, the reader is directed to other excellent reviews (Hanisch, ; Reyes et al, ).…”

Section: Targeting Mononuclear Phagocytes In Retinal Degenerative Dismentioning

confidence: 99%

“…By investigating these cells, the authors found that microglia migrate to the photoreceptor outer segments while monocyte‐derived macrophages appear throughout the entire retina (Reyes et al, ). For further insights into microglia heterogeneity, the reader is directed to other excellent reviews (Hanisch, ; Reyes et al, ).…”

Section: Targeting Mononuclear Phagocytes In Retinal Degenerative Dismentioning

confidence: 99%

Modulation of three key innate immune pathways for the most common retinal degenerative diseases

et al. 2018

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This review highlights the role of three key immune pathways in the pathophysiology of major retinal degenerative diseases including diabetic retinopathy, age‐related macular degeneration, and rare retinal dystrophies. We first discuss the mechanisms how loss of retinal homeostasis evokes an unbalanced retinal immune reaction involving responses of local microglia and recruited macrophages, activity of the alternative complement system, and inflammasome assembly in the retinal pigment epithelium. Presenting these key mechanisms as complementary targets, we specifically emphasize the concept of immunomodulation as potential treatment strategy to prevent or delay vision loss. Promising molecules are ligands for phagocyte receptors, specific inhibitors of complement activation products, and inflammasome inhibitors. We comprehensively summarize the scientific evidence for this strategy from preclinical animal models, human ocular tissue analyses, and clinical trials evolving in the last few years.

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mentioning

confidence: 99%

“…For one, it is the only barrier site that also doubles as an immune privileged tissue (Reyes et al, 2017). Immune privilege is thought to be an evolutionary adaptation that protects the delicate structures of the eye from otherwise deleterious immune responses induced by Fas/Fas ligand (Griffith et al, 1995) and other mediators (Reyes et al, 2017). But this adaptation comes at a price, as immune privilege is also thought to also render the eye vulnerable to certain infections and tumors, which is why J. Wayne Streilein previously referred to eye immune privilege as the “Faustian Dilemma” (Streilein, 1996).…”

mentioning

confidence: 99%