Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy

Ritter, Matthew R.; Banin, Eyal; Moreno, Sandra; Aguilar, Edith; Dorrell, Michael I.; Friedlander, Martin

doi:10.1172/jci29683

Cited by 242 publications

(262 citation statements)

References 45 publications

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“…50 In the second phase, microglia provide cytotrophic support by releasing anti-inflammatory cytokines that promote axon regeneration. 51 Therefore, we selected 7 days as our first time point to evaluate the existence of the hydrogel after acute inflammation.…”

Section: Discussionmentioning

confidence: 99%

Implantable amyloid hydrogels for promoting stem cell differentiation to neurons

et al. 2016

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We report a new class of amyloid-inspired peptide hydrogels that was designed and based on α-synuclein protein for which hydrogel formation is triggered by various stimuli, such as heating/cooling or changes in pH. The peptides resemble a cross-β-sheet-rich amyloid, and they assemble into a nanofibrous meshwork that mimics the natural extracellular matrix. Our design principle allows easy manipulation of the gelator sequence to exploit the desirable properties of amyloids for use in cell replacement therapies for neurodegenerative diseases. The amyloid hydrogels facilitate the attachment and neuronal differentiation of mesenchymal stem cells (MSCs) and assist in the delivery and engraftment of MSCs in the substantia nigra and caudate putamen of a Parkinsonian mouse model.

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Section: Discussionmentioning

confidence: 99%

Implantable amyloid hydrogels for promoting stem cell differentiation to neurons

et al. 2016

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“…EPA, DHA and their potent bioactive products (NPD1, RvD1 and RvE1) at physiological levels reduce pathologic neovascularization through enhanced vessel regrowth after vascular loss and injury. Macrophages or microglia are a critical component of retinal vascular growth and repair 21,22 . In the retina, increased dietary ω-6-PUFA (arachidonic acid) increases activated microglial production of TNF-α, which is suppressed with elevated ω-3-PUFA levels (DHA, EPA).…”

Section: Author Manuscriptmentioning

confidence: 99%

“…Although several cell types can produce TNF-α, monocyte-derived cells are a major source 20 . Microglia, macrophages and dendritic cells are Csf1r + inflammatory cells that are critical to the development and repair of the retinal vasculature 21,22 . To determine whether these cells or vascular endothelial cells produce TNF-α in retinopathy, we immunohistochemically labeled and localized TNF-α, Csf1r and vascular endothelial cells with confocal microscopy in retinal whole-mounts from mice on an ω-6-PUFA diet (Fig.…”

mentioning

confidence: 99%

Increased dietary intake of ω-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis

Connor

SanGiovanni

Löfqvist

et al. 2007

Nat Med

628

572

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Many sight-threatening diseases have two critical phases, vessel loss followed by hypoxia-driven destructive neovascularization. These diseases include retinopathy of prematurity and diabetic retinopathy, leading causes of blindness in childhood and middle age affecting over 4 million people in the United States. We studied the influence of ω-3-and ω-6-polyunsaturated fatty acids (PUFAs) on vascular loss, vascular regrowth after injury, and hypoxia-induced pathological neovascularization in a mouse model of oxygen-induced retinopathy 1 . We show that increasing ω-3-PUFA tissue levels by dietary or genetic means decreased the avascular area of the retina by Reprints and permissions information is available online at http://npg.nature.com/reprintsandpermissionsCorrespondence should be addressed to L.E.H.S. (lois.smith@childrens.harvard.edu).. Supplementary information is available on the Nature Medicine website. COMPETING INTERESTS STATEMENTThe authors declare competing financial interests: details accompany the full-text HTML version of the paper at http:// www.nature.com/naturemedicine/. HHS Public AccessAuthor manuscript Nat Med. Author manuscript; available in PMC 2015 July 05. Published in final edited form as:Nat Med. 2007 July ; 13(7): 868-873. doi:10.1038/nm1591. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript increasing vessel regrowth after injury, thereby reducing the hypoxic stimulus for neovascularization. The bioactive ω-3-PUFA-derived mediators neuroprotectinD1, resolvinD1 and resolvinE1 also potently protected against neovascularization. The protective effect of ω-3-PUFAs and their bioactive metabolites was mediated, in part, through suppression of tumor necrosis factor-α. This inflammatory cytokine was found in a subset of microglia that was closely associated with retinal vessels. These findings indicate that increasing the sources of ω-3-PUFA or their bioactive products reduces pathological angiogenesis. Western diets are often deficient in ω-3-PUFA, and premature infants lack the important transfer from the mother to the infant of ω-3-PUFA that normally occurs in the third trimester of pregnancy 2 . Supplementing ω-3-PUFA intake may be of benefit in preventing retinopathy.Ocular neovascularization is the most common cause of blindness in all age groups: retinopathy of prematurity in children, diabetic retinopathy in working-age adults and agerelated macular degeneration in the elderly. In principle, destructive angiogenesis in the eye can be ameliorated by either direct inhibition of neovascularization or by controlling vessel loss in order to reduce the hypoxic stimulus that drives neovascularization. Retinopathy is modeled in the mouse eye with oxygen-induced vessel loss, which precipitates hypoxiainduced retinopathy, allowing for assessment of retinal vessel loss, vessel regrowth after injury and pathological angiogenesis 1 .The role of lipids in angiogenesis is just beginning to be defined 3,4 . The major polyunsaturated fatty acids (PUFA) found in the retina a...

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“…Restoration of vasculature located on the inner retinal surface by BMSCs is a rational approach toward rescue of retinal neurons lost in retinal vascular disorders, such as diabetic retinopathy [52][53][54]. Injection of BMSCs into the eye improves retinal circulation, enhances survival of outer retinal neurons, and rescues vision in both ischemic and nonischemic mouse models of retinal degeneration [53,55]. These findings open a new paradigm for the relationship between vasculature and the neural retina in which neurotrophic effects secondary to improved circulation after BMSC transplantation benefits both ischemic and nonischemic retinal degenerations [56,57].…”

Section: Non-neural Stem Cellsmentioning

confidence: 99%

Stem Cells for Retinal Replacement Therapy

Stern

Temple

2011

Neurotherapeutics

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Retinal degenerative disease has limited therapeutic options and the possibility of stem cell-mediated regenerative treatments is being actively explored for these blinding retinal conditions. The relative accessibility of this central nervous system tissue and the ability to visually monitor changes after transplantation make the retina and adjacent retinal pigment epithelium prime targets for pioneering stem cell therapeutics. Prior work conducted for several decades indicated the promise of cell transplantation for retinal disease, and new strategies that combine these established surgical approaches with stem cell-derived donor cells is ongoing. A variety of tissue-specific and pluripotent-derived donor cells are being advanced to replace lost or damaged retinal cells and/or to slow the disease processes by providing neuroprotective factors, with the ultimate aim of long-term improvement in visual function. Clinical trials are in the early stages, and data on safety and efficacy are widely anticipated. Positive outcomes from these stem cell-based clinical studies would radically change the way that blinding disorders are approached in the clinic.

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Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy

Cited by 242 publications

References 45 publications

Implantable amyloid hydrogels for promoting stem cell differentiation to neurons

Implantable amyloid hydrogels for promoting stem cell differentiation to neurons

Increased dietary intake of ω-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis

Stem Cells for Retinal Replacement Therapy

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