Introduction of Non-Human Primate (NHP) Models of Laser-Induced Choroidal Neovascularization (CNV)

Age-related macular degeneration (AMD), a highly complex disease, is the leading cause of irreversible blindness in older adults. Choroidal neovascularization (CNV) causes severe central vision loss in 90% of neovascular/exudative (wet) AMD. CNV involves the invasion of new blood vessels from the choroid through the rupture of Bruch's membrane into the subretinal pigment epithelium and subretinal space. Currently, antibody-based inhibitors of vascular endothelial growth factor (VEGF) have emerged as effective treatments for AMD, resulting in clinically significant improvements in VA in many patients. Laser-induced CNV models in nonhuman primates (NHPs) have played a vital role in the development of effective AMD drugs. This model, which uses laser-induced CNV lesions with significant angiographic leakage, is a reliable and reproducible model that has been widely used and well-characterized by researchers. Due to the anatomical similarities between NHP and the human eye, the Rhesus monkey model is relevant for preclinical pharmacology studies and has become the model of choice for preclinical efficacy and safety evaluation of VEGF inhibitors.

Fig. 1. Representative optical coherence tomography (OCT) images for vehicle, bevacizumab and PRO-169 on pre-laser induction, pre-treatment, Days 14 and 28 after intravitreal injection. (Olvera-Montaño O, et al., 2019)

Service Overview

Ace Therapeutics is a fast-growing developer of eye disease models. Our scientists have worked hard to develop a variety of different eye disease models to meet researchers' needs over the years. Here, we are pleased to offer you a non-human primate (NHP) model of laser-induced choroidal neovascularization (CNV).

You can use our NHP model of laser-induced CNV to assess the efficacy of anti-neovascular interventions, which can help you accurately predict your candidate's comparative clinical efficacy against the standard of care for wet age-related macular degeneration (AMD) with anti-VEGF therapy.

Explore Ace Therapeutics' Non-Human Primate (NHP) Models of Laser-Induced Choroidal Neovascularization (CNV)

Ace Therapeutics' scientists establish an NHP model of CNV by laser photocoagulation of the perimacular region of the Rhesus monkey eyes.

• Protocol to Induce a Non-Human Primate (NHP) Model of Laser-Induced Choroidal Neovascularization (CNV)

The following series of ophthalmologic examinations were performed prior to the laser to rule out subjects who did not meet the criteria during the modeling period.

• Indirect ophthalmoscopy.
• Slit lamp microscopy.
• Fundus examination.
• Anterior segment and intraocular pressure (IOP).

Ace Therapeutics' high-quality researchers perform laser treatment on 9 points around the macula of both eyes of Rhesus monkeys that met the criteria. The laser damage was placed around the macula in a circular manner, about one disc diameter from the center of the fovea. The follow-up period is 21 days.

Laser parameters: laser wavelength 532 nm, spot diameter 50 μm, laser power 500-600 mW, exposure time 0.05-0.1s.

Model characteristics: After 20 days of laser photocoagulation, hyperreflective light echogenic masses and fluorescein leakage were found in monkey eyes, and the retinal thickness of the laser spot increased, all of which represented CNV formation.

• Protocols for Testing the Efficacy of Testing Anti-Angiogenic Therapies

Given our unparalleled experience in ophthalmic pharmacology, our ophthalmic pharmacologists have also developed a standardized protocol for testing anti-neovascular interventions for therapeutics.

• Slit lamp microscopy.
• Laser photocoagulation injury.
• Vitreous injection of drugs behind the eye.

Our Capabilities

In order to accurately characterize the biological function of laser-induced CNV rhesus monkeys and assess the safety and efficacy of candidate therapies, our researchers provide a variety of analytical services, including but not limited to:

• Multifocal electroretinogram analysis.
• Optical coherence tomography (OCT) examination.
• Color photography and fluorescein fundus angiography.
• Histopathologic and immunohistochemistry analysis.
• Molecular biology analysis.

Ace Therapeutics aims to provide a valuable tool to help our global customers predict clinical responses to anti-angiogenic therapy for ophthalmic products. If you are interested in our services or need more detailed information, please feel free to contact us. Our experienced scientists are ready to help you!

References

1. Olvera-Montaño O, Baiza-Duran L, Quintana-Hau JD, et al. Comparing The Efficacy Of An Anti-Human VEGF-A Neutralizing Antibody Versus Bevacizumab On A Laser-Induced Choroidal Neovascularization (CNV) Rhesus Monkey Model. Drug Des Devel Ther. 2019, 13:3813-3821.
2. Zhang M, Zhang J, Yan M, Li H, Yang C, Yu D. Recombinant anti-vascular endothelial growth factor fusion protein efficiently suppresses choridal neovasularization in monkeys. Mol Vis. 2008, 14:37-49.
3. Lukason M, DuFresne E, Rubin H, et al. Inhibition of choroidal neovascularization in a nonhuman primate model by intravitreal administration of an AAV2 vector expressing a novel anti-VEGF molecule. Mol Ther. 2011, 19(2):260-5.

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