Mobile Laser Indirect Ophthalmoscope: For the Induction of Choroidal Neovascularization in a Mouse Model

Weinberger, Dov; Bor-Shavit, Elite; Barliya, Tilda; Dahbash, Mor; Kinrot, Opher; Gaton, Dan D.; Nisgav, Yael; Livnat, Tami

doi:10.1080/02713683.2017.1349154

Cited by 8 publications

(9 citation statements)

References 28 publications

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“…Next, we induced CNV in the eye by laser treatment 6 weeks after injection of AAV-Cpf1- Vegfa or - Hif1a and measured the area of CNV 25 1 week later (Fig. 3a ).…”

Section: Resultsmentioning

confidence: 99%

CRISPR-LbCpf1 prevents choroidal neovascularization in a mouse model of age-related macular degeneration

Koo

Park

et al. 2018

Nat Commun

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LbCpf1, derived from Lachnospiraceae bacterium ND2006, is a CRISPR RNA-guided endonuclease and holds promise for therapeutic applications. Here we show that LbCpf1 can be used for therapeutic gene editing in a mouse model of age-related macular degeneration (AMD). The intravitreal delivery of LbCpf1, targeted to two angiogenesis-associated genes encoding vascular endothelial growth factor A (Vegfa) and hypoxia inducing factor 1a (Hif1a), using adeno-associated virus, led to efficient gene disruption with no apparent off-target effects in the retina and retinal pigment epithelium (RPE) cells. Importantly, LbCpf1 targeted to Vegfa or Hif1a in RPE cells reduced the area of laser-induced choroidal neovascularization as efficiently as aflibercept, an anti-VEGF drug currently used in the clinic, without inducing cone dysfunction. Unlike aflibercept, LbCpf1 targeted to Vegfa or Hif1a achieved a long-term therapeutic effect on CNV, potentially avoiding repetitive injections. Taken together, these results indicate that LbCpf1-mediated in vivo genome editing to ablate pathologic angiogenesis provides an effective strategy for the treatment of AMD and other neovascularization-associated diseases.

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“…Next, we induced CNV in the eye by laser treatment 6 weeks after injection of AAV-Cpf1- Vegfa or - Hif1a and measured the area of CNV 25 1 week later (Fig. 3a ).…”

Section: Resultsmentioning

confidence: 99%

CRISPR-LbCpf1 prevents choroidal neovascularization in a mouse model of age-related macular degeneration

Koo

Park

et al. 2018

Nat Commun

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“…The current efficacious treatments for CNV are mostly based on anti-VEGF agents, yet, suboptimal response, slow loss of efficacy, and long term concerns regarding the continuity of the neurodegenerative process restricted their full success [1,2,23]. Using the laser-induced CNV mouse model, we previously demonstrated that APC treatment reduced CNV to a similar extent as bevacizumab [7,13].…”

Section: Discussionmentioning

confidence: 99%

“…All animal experiments were performed according to the Association for Research in Vision and Ophthalmology (ARVO) statement's guidelines for the Use of Animals in Ophthalmic and Visual Research and the approval of the Institutional Animal Care and Use Committee at Rabin Medical Center. CNV was induced based on Weinberger et al [13] as previously described [7]. Briefly, diode laser indirect ophthalmoscope (Iris Medical Oculight SLX System©, Iridex, Mountain View, CA, USA) was used with a laser power of 350 mW for a duration of 100 msec and a condensing lens of 90 diopters.…”

Section: In Vivo Laser-induced Cnv Animal Modelmentioning

confidence: 99%

Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction

et al. 2021

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The activated protein C (APC) ability to inhibit choroidal neovascularization (CNV) growth and leakage was recently shown in a murine model. A modified APC, 3K3A-APC, was designed to reduce anticoagulant activity while maintaining full cytoprotective properties, thus diminishing bleeding risk. We aimed to study the ability of 3K3A-APC to induce regression of CNV and evaluate vascular endothelial growth factor (VEGF) role in APC’s activities in the retina. CNV was induced by laser photocoagulation on C57BL/6J mice. APC and 3K3A-APC were injected intravitreally after verification of CNV presence. CNV volume and vascular penetration were evaluated on retinal pigmented epithelium (RPE)-choroid flatmount by fluorescein isothiocyanate (FITC)-dextran imaging. VEGF levels were measured using immunofluorescence anti-VEGF staining. We found that 3K3A-APC induced regression of pre-existing CNV. VEGF levels, measured in the CNV lesion sites, significantly decreased upon APC and 3K3A-APC treatment. Reduction in VEGF was sustained 14 days post a single APC injection. As 3K3A-APC retained APCs’ activities, we conclude that the anticoagulant properties of APC are not mandatory for APC activities in the retina and that VEGF reduction may contribute to the protective effects of APC and 3K3A-APC. Our results highlight the potential use of 3K3A-APC as a novel treatment for CNV and other ocular pathologies.

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“…CNV was performed as previously described by Weinberger et al [65] Briefly, diode laser indirect ophthalmoscope (Iris Medical Oculight SLX System©, Iridex, Mountain View, CA, USA) was used with laser power of 350 mW for duration of 100 msec, and a condensing lens of 90 diopters. Three laser applications were applied on the right eye, at a distance of 1 to 2 optic disc diameters around the optic nerve.…”

Section: Methodsmentioning

confidence: 99%

The Histone Deacetylase Inhibitor AN7, Attenuates Choroidal Neovascularization in a Mouse Model

Dahbash

Sella

Megiddo-Barnir

et al. 2019

IJMS

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: Choroidal neovascularization (CNV) is a complication of age-related macular degeneration and a major contributing factor to vision loss. In this paper, we show that in a mouse model of laser-induced CNV, systemic administration of Butyroyloxymethyl-diethyl phosphate (AN7), a histone deacetylase inhibitor (HDACi), significantly reduced CNV area and vascular leakage, as measured by choroidal flatmounts and fluorescein angiography. CNV area reduction by systemic AN7 treatment was similar to that achieved by intravitreal bevacizumab treatment. The expression of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF-2), and the endothelial cells marker CD31, was lower in the AN7 treated group in comparison to the control group at the laser lesion site. In vitro, AN7 facilitated retinal pigmented epithelium (RPE) cells tight junctions’ integrity during hypoxia, by protecting the hexagonal pattern of ZO-1 protein in the cell borders, hence reducing RPE permeability. In conclusion, systemic AN7 should be further investigated as a possible effective treatment for CNV.

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Mobile Laser Indirect Ophthalmoscope: For the Induction of Choroidal Neovascularization in a Mouse Model

Abstract: The mobile laser indirect ophthalmoscope can serve as a feasible and a reliable alternative method for the CNV induction in a mouse model.

Cited by 8 publications

References 28 publications

CRISPR-LbCpf1 prevents choroidal neovascularization in a mouse model of age-related macular degeneration

CRISPR-LbCpf1 prevents choroidal neovascularization in a mouse model of age-related macular degeneration

Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction

The Histone Deacetylase Inhibitor AN7, Attenuates Choroidal Neovascularization in a Mouse Model

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