Paracrine Modulation of CXCR4 by IGF-1 and VEGF: Implications for Choroidal Neovascularization

Sengupta, Nilanjana; Afzal, Aqeela; Caballero, Sergio; Chang, Kyung Hee; Shaw, Lynn C.; Pang, Ji; Bond, Vincent C.; Bhutto, Imran Ahmed; Baba, Takayuki; Lutty, Gerard A.; Grant, Maria B.

doi:10.1167/iovs.09-4137

Cited by 35 publications

(38 citation statements)

References 34 publications

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“…The model is applicable to transgenic (knock-out or knock-in) mice. In addition, viruses, cells or compounds, including neutralizing antibodies, si/shRNA, pre-miR, recombinant proteins, nanoparticles and drugs, can be administered via different pathways (intraperitoneal injection, intravenous injection, per os, drinking water, intravitreous injection, subretinal injection, BM engraftment and others) and combined or not with genetic manipulation 9,[33][34][35][36][37] .…”

Section: Applications Of the Cnv Assaymentioning

confidence: 99%

Laser-induced choroidal neovascularization model to study age-related macular degeneration in mice

et al. 2013

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The mouse model of laser-induced choroidal neovascularization (CNV) has been used extensively in studies of the exudative form of age-related macular degeneration (AMD). This experimental in vivo model relies on laser injury to perforate Bruch's membrane, resulting in sub-retinal blood vessel recruitment from the choroid. By recapitulating the main features of the exudative form of human AMD, this assay has served as the backbone for testing antiangiogenic therapies. This standardized protocol can be applied to transgenic mice and can include treatments with drugs, recombinant proteins, antibodies, adenovirus and pre-miR to aid in the search for new molecular regulators and the identification of novel targets for innovative treatments. This robust assay requires 7-14 days to complete, depending on the treatment applied and whether immunostaining is performed. This protocol includes details of 2 how to induce CNV, including laser induction, lesion excision, processing plus different approaches to quantify neoformed vasculature.

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Section: Applications Of the Cnv Assaymentioning

confidence: 99%

Laser-induced choroidal neovascularization model to study age-related macular degeneration in mice

et al. 2013

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“…28,29 Briefly, eyes were dilated using 1% tropicamide, then underwent laser treatment using 50 mm spot size, 50 ms duration, and 250 mV pulses of an ophthalmic argon green laser, wavelength 532 nm, coupled to a slit lamp. A coverslip was used to allow viewing of the posterior pole of the eye.…”

Section: Laser-induced Model Of Cnvmentioning

confidence: 99%

A Simple Optical Coherence Tomography Quantification Method for Choroidal Neovascularization

Sulaiman

Quigley

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

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Purpose: Therapeutic efficacy is routinely assessed by measurement of lesion size using flatmounted choroids and confocal microscopy in the laser-induced choroidal neovascularization (L-CNV) rodent model. We investigated whether optical coherence tomography (OCT) quantification, using an ellipsoid volume measurement, was comparable to standard ex vivo evaluation methods for this model and whether this approach could be used to monitor treatment-related lesion changes. Methods: Bruch's membrane was ruptured by argon laser in the dilated eyes of C57BL/6J mice, followed by intravitreal injections of anti-VEGF 164 or vehicle, or no injection. In vivo OCT images were acquired using Micron III or InVivoVue systems at 7, 10, and/or 14 days post-laser and neovascular lesion volume was calculated as an ellipsoid. Subsequently, lesion volume was compared to that calculated from confocal Z-stack images of agglutinin-stained choroidal flatmounts. Results: Ellipsoid volume measurement of orthogonal 2-dimensional OCT images obtained from different imaging systems correlated with ex vivo lesion volumes for L-CNV (Spearman's r = 0.82, 0.75, and 0.82 at days 7, 10, and 14, respectively). Ellipsoid volume calculation allowed temporal monitoring and evaluation of CNV lesions in response to antivascular endothelial growth factor treatment. Conclusions: Ellipsoid volume measurements allow rapid, quantitative use of OCT for the assessment of CNV lesions in vivo. This novel method can be used with different OCT imaging systems with sensitivity to distinguish between treatment conditions. It may serve as a useful adjunct to the standard ex vivo confocal quantification, to assess therapeutic efficacy in preclinical models of CNV, and in models of other ocular diseases.

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“…10,29 Among the 11 molecules, CCL2/CCR2, CXCL12/CXCR4, and CCL11 were already reported to have some effects on CNV. [6][7][8][9] Therefore, in the current study, interest was focused on CXCR3 and one of its ligands, CXCL10 (IP-10), because to the best of the authors' knowledge, their role in CNV development had never been investigated, and it has been suggested that CXCR3 is relevant to angiostasis in previous studies. [30][31][32][33] Expression of CXCR3 and Three Major Ligands in CNV CXCR3 is one of the mammalian chemokine receptors, promoting chemotaxis and cell proliferation, binding with its three major chemokines: IP-10, MIG, and I-TAC.…”

Section: Microarray Analysis Of Chemokines or Chemokine Receptors In Cnvmentioning

confidence: 99%

“…CC and CXC are two major structural variants that differ according to variations in a shared cysteine (C) motif. Accumulating laboratory evidence suggests that chemokines and chemokine receptors, such as CCL2/CCR2, 6 CX3CL1/ CX3CR1, 7 CCR3, 8 and CXCR4 9 are involved in CNV. The CXC chemokine family has four highly conserved cysteine amino acid residues, with the first two cysteines separated by a nonconserved amino acid residue.…”

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confidence: 99%

Angiostatic Effect of CXCR3 Expressed on Choroidal Neovascularization

Fujimura

Takahashi²,

Yuda³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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Paracrine Modulation of CXCR4 by IGF-1 and VEGF: Implications for Choroidal Neovascularization

Abstract: The potent proangiogenic factors IGF-1 and VEGF both stimulate SDF-1-induced angiogenesis. Local inhibition of CXCR4 is required for an antiangiogenic effect in CNV lesions.

Cited by 35 publications

References 34 publications

Laser-induced choroidal neovascularization model to study age-related macular degeneration in mice

Laser-induced choroidal neovascularization model to study age-related macular degeneration in mice

A Simple Optical Coherence Tomography Quantification Method for Choroidal Neovascularization

Angiostatic Effect of CXCR3 Expressed on Choroidal Neovascularization

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