Brain and Retinal Pericytes: Origin, Function and Role

Trost, Andrea; Lange, Simona; Schroedl, Falk; Bruckner, Daniela; Motloch, Karolina; Bogner, Barbara; Kaser-Eichberger, Alexandra; Strohmaier, Clemens; Runge, Christian; Aigner, Ludwig; Rivera, Francisco J.; Reitsamer, Herbert A.

doi:10.3389/fncel.2016.00020

Cited by 198 publications

(168 citation statements)

References 140 publications

(178 reference statements)

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“…The retina is a CNS tissue originating in the developing diencephalon, and it contains high-density neuronal cells and fibers that form a sensory extension of the brain [25]. It also shares many structural and functional features with the brain, including the presence of neurons, glial cells, a blood barrier, and similar cell-fate specification of embryonically related tissues as well as tight regulation of endothelial cell proliferation [25, 126, 176]. Furthermore, axons of the optic nerve connect the retina to the brain directly and facilitate the transportation of AβPP synthesized in RGCs in small transport vesicles [136].…”

Section: Introductionmentioning

confidence: 99%

Ocular indicators of Alzheimer’s: exploring disease in the retina

et al. 2016

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Although historically perceived as a disorder confined to the brain, our understanding of Alzheimer’s disease (AD) has expanded to include extra-cerebral manifestation, with mounting evidence of abnormalities in the eye. Among ocular tissues, the retina, a developmental outgrowth of the brain, is marked by an array of pathologies in patients suffering from AD, including nerve fiber layer thinning, degeneration of retinal ganglion cells, and changes to vascular parameters. While the hallmark pathological signs of AD, amyloid β-protein (Aβ) plaques and neurofibrillary tangles (NFT) comprising hyperphosphorylated tau (pTau) protein, have long been described in the brain, identification of these characteristic biomarkers in the retina has only recently been reported. In particular, Aβ deposits were discovered in post-mortem retinas of advanced and early stage cases of AD, in stark contrast to non-AD controls. Subsequent studies have reported elevated Aβ42/40 peptides, morphologically diverse Aβ plaques, and pTau in the retina. In line with the above findings, animal model studies have reported retinal Aβ deposits and tauopathy, often correlated with local inflammation, retinal ganglion cell degeneration, and functional deficits. This review highlights the converging evidence that AD manifests in the eye, especially in the retina, which can be imaged directly and non-invasively. Visual dysfunction in AD patients, traditionally attributed to well-documented cerebral pathology, can now be reexamined as a direct outcome of retinal abnormalities. As we continue to study the disease in the brain, the emerging field of ocular AD warrants further investigation of how the retina may faithfully reflect the neurological disease. Indeed, detection of retinal AD pathology, particularly the early presenting amyloid biomarkers, using advanced high-resolution imaging techniques may allow large-scale screening and monitoring of at-risk populations.

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Section: Introductionmentioning

confidence: 99%

Ocular indicators of Alzheimer’s: exploring disease in the retina

et al. 2016

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“…However, definition of PC by criteria that requires ultrastructural analysis for identification is not practical (6). Currently, at least two markers (positive reactivity to both PDGFR-β and NG2 being widely accepted) as well as morphology and cell location (in close contact with EC, embedded in the same basement membrane) are required to unequivocally distinguish PC from other mesenchymal cells (7). The use of transgenic mouse models fluorescently labeling PC [e.g., NG2-dsRed (8), the inducible NG2-CreERT2-eGFP (9), αSMA-GFP or αSMA-mCherry (10), and the double-transgenic nestin-GFP/NG2-DsRed mouse (11)] may be essential for studying the fate of PC under different conditions.…”

Section: Introductionmentioning

confidence: 99%

Immune Regulation by Pericytes: Modulating Innate and Adaptive Immunity

et al. 2016

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Pericytes (PC) are mural cells that surround endothelial cells in small blood vessels. PC have traditionally been credited with structural functions, being essential for vessel maturation and stabilization. However, an accumulating body of evidence suggests that PC also display immune properties. They can respond to a series of pro-inflammatory stimuli and are able to sense different types of danger due to their expression of functional pattern-recognition receptors, contributing to the onset of innate immune responses. In this context, PC not only secrete a variety of chemokines but also overexpress adhesion molecules such as ICAM-1 and VCAM-1 involved in the control of immune cell trafficking across vessel walls. In addition to their role in innate immunity, PC are involved in adaptive immunity. It has been reported that interaction with PC anergizes T cells, which is attributed, at least in part, to the expression of PD-L1. As components of the tumor microenvironment, PC can also modulate the antitumor immune response. However, their role is complex, and further studies will be required to better understand the crosstalk of PC with immune cells in order to consider them as potential therapeutic targets. In any case, PC will be looked at with new eyes by immunologists from now on.

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“…11). In addition to afflicting the brain, AD also affects the retina, a developmental outgrowth of the brain (12)(13)(14), possibly causing these symptoms. The retinas of AD patients display pathologies such as nerve fiber layer (NFL) thinning, retinal ganglion cell (RGC) degeneration, reduction of blood flow and vascular alterations, astrogliosis, and abnormal electroretinogram patterns (11,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33).…”

Section: Introductionmentioning

confidence: 99%

Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease

et al. 2017

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BACKGROUND. Noninvasive detection of Alzheimer's disease (AD) with high specificity and sensitivity can greatly facilitate identification of at-risk populations for earlier, more effective intervention. AD patients exhibit a myriad of retinal pathologies, including hallmark amyloid β-protein (Aβ) deposits. METHODS.Burden, distribution, cellular layer, and structure of retinal Aβ plaques were analyzed in flat mounts and cross sections of definite AD patients and controls (n = 37). In a proof-of-concept retinal imaging trial (n = 16), amyloid probe curcumin formulation was determined and protocol was established for retinal amyloid imaging in live patients. RESULTS.Histological examination uncovered classical and neuritic-like Aβ deposits with increased retinal Aβ 42 plaques (4.7-fold; P = 0.0063) and neuronal loss (P = 0.0023) in AD patients versus matched controls. Retinal Aβ plaque mirrored brain pathology, especially in the primary visual cortex (P = 0.0097 to P = 0.0018; Pearson's r = 0.84-0.91). Retinal deposits often associated with blood vessels and occurred in hot spot peripheral regions of the superior quadrant and innermost retinal layers. Transmission electron microscopy revealed retinal Aβ assembled into protofibrils and fibrils. Moreover, the ability to image retinal amyloid deposits with solid-lipid curcumin and a modified scanning laser ophthalmoscope was demonstrated in live patients. A fully automated calculation of the retinal amyloid index (RAI), a quantitative measure of increased curcumin fluorescence, was constructed. Analysis of RAI scores showed a 2.1-fold increase in AD patients versus controls (P = 0.0031). CONCLUSION.The geometric distribution and increased burden of retinal amyloid pathology in AD, together with the feasibility to noninvasively detect discrete retinal amyloid deposits in living patients, may lead to a practical approach for large-scale AD diagnosis and monitoring.

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Brain and Retinal Pericytes: Origin, Function and Role

Cited by 198 publications

References 140 publications

Ocular indicators of Alzheimer’s: exploring disease in the retina

Ocular indicators of Alzheimer’s: exploring disease in the retina

Immune Regulation by Pericytes: Modulating Innate and Adaptive Immunity

Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease

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