Ocular Neovascularization

Neely, Kimberly A.; Gardner, Thomas W.

doi:10.1016/s0002-9440(10)65607-6

Cited by 51 publications

(27 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The etiology of a number of eye diseases involve activation of immune cells, inflammation, degeneration of neurons, neovascularization and fibrosis (Cousins et al, 2004; Hernandez et al, 1990; Howell et al, 2013; Ishikawa et al, 2016; Neely and Gardner, 1998; Pflugfelder, 2004; Tektas and Lutjen-Drecoll, 2009; Vranka et al, 2015). As discussed in this review, exosomes are likely mediating some, if not all of these effects.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Roles of exosomes in the normal and diseased eye

Klingeborn

Dismuke

Rickman

et al. 2017

Progress in Retinal and Eye Research

148

127

View full text Add to dashboard Cite

Exosomes are nanometer-sized vesicles that are released by cells in a controlled fashion and mediate a plethora of extra- and intercellular activities. Some key functions of exosomes include cell-cell communication, immune modulation, extracellular matrix turnover, stem cell division/differentiation, neovascularization and cellular waste removal. While much is known about their role in cancer, exosome function in the many specialized tissues of the eye is just beginning to undergo rigorous study. Here we review current knowledge of exosome function in the visual system in the context of larger bodies of data from other fields, in both health and disease. Additionally, we discuss recent advances in the exosome field including use of exosomes as a therapeutic vehicle, exosomes as a source of biomarkers for disease, plus current standards for isolation and validation of exosome populations. Finally, we use this foundational information about exosomes in the eye as a platform to identify areas of opportunity for future research studies.

show abstract

Section: Discussionmentioning

confidence: 99%

“…As already discussed, neovascularization underlies a number of eye diseases including neovascular AMD, diabetic retinopathy, macular edema, neovascular glaucoma and corneal neovascularization (Neely and Gardner, 1998). A number of groups have demonstrated anti-angiogenic properties of exosomes.…”

Section: Exosomes As Therapeutic Agentsmentioning

confidence: 99%

Roles of exosomes in the normal and diseased eye

Klingeborn

Dismuke

Rickman

et al. 2017

Progress in Retinal and Eye Research

148

127

View full text Add to dashboard Cite

show abstract

“…For these experiments, we selected the retina as a model system because the retinal vasculature develops postnatally in a stereotypic manner that is highly organized, temporally and spatially (16). Moreover, the murine model of oxygen-induced ischemic retinopathy (OIR) (17) is a well characterized model of pathological neovascularization associated with elevated expression of endogenous proangiogenic factors, including VEGF (18,19), and thus relevant to pathological angiogenesis associated with diverse disease conditions (20). Finally, the retinal vasculature is readily accessible to experimental manipulations, including intravitreal microinjections of experimental agents.…”

mentioning

confidence: 99%

Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting

Lobov

Renard²,

Papadopoulos³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

696

710

View full text Add to dashboard Cite

Genetic deletion studies have shown that haploinsufficiency of Deltalike ligand (Dll) 4, a transmembrane ligand for the Notch family of receptors, results in major vascular defects and embryonic lethality. To better define the role of Dll4 during vascular growth and differentiation, we selected the postnatal retina as a model because its vasculature develops shortly after birth in a highly stereotypic manner, during which time it is accessible to experimental manipulation. We report that Dll4 expression is dynamically regulated by VEGF in the retinal vasculature, where it is most prominently expressed at the leading front of actively growing vessels. Deletion of a single Dll4 allele or pharmacologic inhibition of Dll4/Notch signaling by intraocular administration of either soluble Dll4-Fc or a blocking antibody against Dll4 all produced the same set of characteristic abnormalities in the developing retinal vasculature, most notably enhanced angiogenic sprouting and increased endothelial cell proliferation, resulting in the formation of a denser and more highly interconnected superficial capillary plexus. In a model of ischemic retinopathy, Dll4 blockade also enhanced angiogenic sprouting and regrowth of lost retinal vessels while suppressing ectopic pathological neovascularization. Our data demonstrate that Dll4 is induced by VEGF as a negative feedback regulator and acts to prevent overexuberant angiogenic sprouting, promoting the timely formation of a well differentiated vascular network.angiogenesis ͉ retina ͉ Notch ͉ oxygen-induced retinopathy

show abstract

“…E xcessive formation of new blood vessels in the retina is considered a hallmark of ischemic retinopathies such as diabetic retinopathy, a leading cause of blindness in the United States and Europe. Moreover, ocular neovascularization is considered a common etiological factor in diseases ranging widely in age of onset, from retinopathy of prematurity in oxygen-treated infants, to sickle cell disease and retinal venous occlusions seen in adults, to age-related macular degeneration observed in the elderly (1,2).…”

mentioning

confidence: 99%

An anti-angiogenic state in mice and humans with retinal photoreceptor cell degeneration

Schlingemann

Lahdenranta

Pasqualini

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Abnormal angiogenesis accompanies many pathological conditions including cancer, inflammation, and eye diseases. Proliferative retinopathy because of retinal neovascularization is a leading cause of blindness in developed countries. Another major cause of irreversible vision loss is retinitis pigmentosa, a group of diseases characterized by progressive photoreceptor cell degeneration. Interestingly, anecdotal evidence has long suggested that proliferative diabetic retinopathy is rarely associated clinically with retinitis pigmentosa. Here we show that neonatal mice with classic inherited retinal degeneration (Pdeb rd1 /Pdeb rd1 ) fail to mount reactive retinal neovascularization in a mouse model of oxygeninduced proliferative retinopathy. We also present a comparable human paradigm: spontaneous regression of retinal neovascularization associated with long-standing diabetes mellitus occurs when retinitis pigmentosa becomes clinically evident. Both mouse and human data indicate that reactive retinal neovascularization either fails to develop or regresses when the number of photoreceptor cells is markedly reduced. Our findings support the hypothesis that a functional mechanism underlying this anti-angiogenic state is failure of the predicted up-regulation of vascular endothelial growth factor, although other growth factors may also be involved. Preventive and therapeutic strategies against both proliferative and degenerative retinopathies may emerge from this work.

show abstract

Ocular Neovascularization

Cited by 51 publications

References 46 publications

Roles of exosomes in the normal and diseased eye

Roles of exosomes in the normal and diseased eye

Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting

An anti-angiogenic state in mice and humans with retinal photoreceptor cell degeneration

Contact Info

Product

Resources

About