Semaphorin 3F forms an anti‐angiogenic barrier in outer retina

Buehler, Anima; Sitaras, Nicholas; Favret, Sandra; Bucher, Felicitas; Berger, Sandra L.; Pielen, Amelie; Joyal, Jean-Sebastian; Juan, Aimee M.; Martin, Gottfried; Schlunck, Guenther; Agostini, Hansjürgen; Klagsbrun, Michael; Smith, Lois E.H.; Sapieha, Przemysław; Stahl, Andreas

doi:10.1016/j.febslet.2013.04.008

Cited by 43 publications

(46 citation statements)

References 19 publications

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“…11 It is usually assumed that the diffusion of oxygen from the choroid maintains normoxia of the photoreceptor layer, which inhibits the expression of vasoproliferative agents such as the vascular endothelial growth factor (VEGF). Various angio-inhibitors playing a role in retinal or choroidal neovascularization prevention have been identified in the outer retina.…”

Section: Discussionmentioning

confidence: 99%

Outer Retina Capillary Invasion and Ellipsoid Zone Loss in Macular Telangiectasia Type 2 Imaged by Optical Coherence Tomography Angiography

Gaudric

Krivosic

Tadayoni

2015

Retina

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Section: Discussionmentioning

confidence: 99%

Outer Retina Capillary Invasion and Ellipsoid Zone Loss in Macular Telangiectasia Type 2 Imaged by Optical Coherence Tomography Angiography

Gaudric

Krivosic

Tadayoni

2015

Retina

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“…183 However, these abnormalities can be partially remedied by intra-vitreal injection of Sema3E which was observed to suppress the extra-retinal vascular outgrowth without affecting the desired regeneration of the retinal vasculature. 184 In addition it was recently observed that the avascular characteristic of the outer layers of the retina is due to the expression of sema3F in cells in these outer layers, 185 suggesting that several different semaphorins acting in concert regulate the distribution of blood vessels in the normal and diseased retina. In the context of cancer it was observed that ectopic overexpression of sema3E in a variety of tumor cell types inhibits tumor development from such cells.…”

Section: 178mentioning

confidence: 99%

The role of the semaphorins in cancer

Neufeld

Mumblat

Smolkin

et al. 2016

Cell Adhesion & Migration

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The semaphorins were initially characterized as axon guidance factors, but have subsequently been implicated also in the regulation of immune responses, angiogenesis, organ formation, and a variety of additional physiological and developmental functions. The semaphorin family contains more then 20 genes divided into 7 subfamilies, all of which contain the signature sema domain. The semaphorins transduce signals by binding to receptors belonging to the neuropilin or plexin families. Additional receptors which form complexes with these primary semaphorin receptors are also frequently involved in semaphorin signaling. Recent evidence suggests that semaphorins also fulfill important roles in the etiology of multiple forms of cancer. Some semaphorins have been found to function as bona-fide tumor suppressors and to inhibit tumor progression by various mechanisms while other semaphorins function as inducers and promoters of tumor progression. The semaphorin familyThe semaphorin family members are divided into 8 subclasses of which subclasses 1 and 2 contain invertebrate semaphorins while subclasses 3-7 contain the 22 vertebrate semaphorins. The 8th subclass contains viral semaphorins. In early publications, semaphorins were assigned confusing names. This situation was rectified by the adoption of a unified nomenclature in which sema is followed by the subclass number and by alphabetic designation within the subclass.1 Semaphorins are characterized by the presence of a »500 amino-acids long sema domain located close to their N-termini which is also present in semaphorin receptors of the plexin family, and by a plexin-semaphorin-integrin (PSI) domain located downstream to the sema domain. The sema domain is essential for semaphorin activity and plays a role in the determination of the receptor binding specificity.2 The sema domains of several different semaphorins were characterized by X-ray crystallography revealing a b propeller topology.3-5 Different semaphorin subclasses are characterized by class specific structural motifs. Thus, the vertebrate semaphorins belonging to classes 3, 4 and 7 contain immunoglobulin like domains, class-5 semaphorins contain thrombospondin repeats and class-3 semaphorins contain a basic domain. Class-3 semaphorins are the only vertebrate semaphorins produced as secreted proteins while other vertebrate semaphorins are membrane anchored or trans-membrane proteins that can be further processed into soluble forms by proteolytic cleavage (Fig.

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“…SEMA3s are all secreted proteins and include 7 members (SEMA3A-G). In the retina, Sema3A, E and F were reported as vaso-repulsive cues in developmental retinal angiogenesis (10)(11)(12). In addition, SEMA-3A, C, and E are all involved in pathological retinal neovascularization in eye disease models (13)(14)(15).…”

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confidence: 99%

RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis

et al. 2017

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Pathological proliferation of retinal blood vessels commonly causes vision impairment in proliferative retinopathies, including retinopathy of prematurity. Dysregulated crosstalk between the vasculature and retinal neurons is increasingly recognized as a major factor contributing to the pathogenesis of vascular diseases. Class 3 semaphorins (SEMA3s), a group of neuron-secreted axonal and vascular guidance factors, suppress pathological vascular growth in retinopathy. However, the upstream transcriptional regulators that mediate the function of SEMA3s in vascular growth are poorly understood. Here we showed that retinoic acid receptor-related orphan receptor a (RORa), a nuclear receptor and transcription factor, is a novel transcriptional regulator of SEMA3E-mediated neurovascular coupling in a mouse model of oxygen-induced proliferative retinopathy. We found that genetic deficiency of RORa substantially induced Sema3e expression in retinopathy. Both RORa and SEMA3E were expressed in retinal ganglion cells. RORa directly bound to a specific ROR response element on the promoter of Sema3e and negatively regulated Sema3e promoter-driven luciferase expression. Suppression of Sema3e using adeno-associated virus 2 carrying short hairpin RNA targeting Sema3e promoted disoriented pathological neovascularization and partially abolished the inhibitory vascular effects of RORa deficiency in retinopathy. Our findings suggest that RORa is a novel transcriptional regulator of SEMA3E-mediated neurovascular coupling in pathological retinal angiogenesis.-Sun, Y., Liu, C.-H., Wang, Z., Meng, S. S., Burnim, S. B., SanGiovanni, J. P., Kamenecka, T. M., Solt, L. A., Chen, J. RORa modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis. FASEB J. 31, 4492-4502 (2017). www.fasebj.org

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Semaphorin 3F forms an anti‐angiogenic barrier in outer retina

Cited by 43 publications

References 19 publications

Outer Retina Capillary Invasion and Ellipsoid Zone Loss in Macular Telangiectasia Type 2 Imaged by Optical Coherence Tomography Angiography

Outer Retina Capillary Invasion and Ellipsoid Zone Loss in Macular Telangiectasia Type 2 Imaged by Optical Coherence Tomography Angiography

The role of the semaphorins in cancer

RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis

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