Optimization of laser-induced choroidal neovascularization in African green monkeys

Goody, Robin J; Hu, Wenzheng; Shafiee, Afshin; Struharik, Michael; Bartels, S P; López, Francisco J.; Lawrence, Matthew S.

doi:10.1016/j.exer.2011.03.006

Cited by 39 publications

(47 citation statements)

References 24 publications

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“…23 Monkeys were anesthetized with ketamine (8 mg/kg) and xylazine (1.6 mg/kg) for all procedures. Topical twice-daily dosing with 54 L aganirsen or vehicle (ophthalmic emulsion composed of carbomer, caprylic/capric acid triglycerides, cetyl alcohol, glycerol and polyethylene glycol stearates, sodium hydroxide, and water) was initiated 2 days before laser photocoagulation.…”

Section: Laser-induced Cnv In Nonhuman Primatesmentioning

confidence: 99%

“…On day 1, in both eyes of all 26 study monkeys, six laser spots were concentrically spaced approximately 1.5 disc diameters from the fovea at the anatomic periphery of the macula, within the temporal vascular arcades, as previously described. 23 Fundus photographs were taken immediately before and immediately after laser photocoagulation in each eye. Fundus images and angiograms were collected on the left eye (OS) and then the right eye (OD) on day 29 (week 4) after laser photocoagulation using a retinal camera (TRC-50ϫ; Topcon, Tokyo, Japan) with digital imaging hardware (Canon 5D; Canon, Tokyo, Japan) and imaging software (New Vision Image Analysis System; Fundus Photo, St. Louis, MO).…”

Section: Laser-induced Cnv In Nonhuman Primatesmentioning

confidence: 99%

“…At each lesion site, the extent of late-phase fluorescein leakage, an angiographic change associated with CNV, was rated as described previously 23 on a scale of I to IV. Scoring was conducted by two investigators who remained masked to treatment group.…”

Section: Fluorescein Angiography Scoringmentioning

confidence: 99%

“…23 Quantitative CNV scoring was applied to acquired OCT images by definition of the principal axis of maximal CNV complex formation within each star-shaped scan at each laser lesion by a masked evaluator. The CNV complex area in the OCT image in that axis was then measured using the freehand tool within ImageJ to delineate the CNV complex boundary and to calculate maximum complex area in square micrometers (m 2 ).…”

Section: Imagej Analysis Of Angiograms and Oct Imagesmentioning

confidence: 99%

“…The effect of aganirsen was dose dependent, but these changes were not significant at lower doses (43 g, P ϭ 0.08; 21.5 g, P ϭ 0.09). Our previous work in African green monkeys 23 and other nonhuman primate laserinduced CNV models 28 has demonstrated that clinically relevant CNV in nonhuman primates applies to grade III and grade IV lesions. 23,28 The incidence of grade III lesions alone ( Fig.…”

Section: Aganirsen Reduces Pathologic Neovascularization In a Primatementioning

confidence: 99%

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Antiangiogenic Activity of Aganirsen in Nonhuman Primate and Rodent Models of Retinal Neovascular Disease after Topical Administration

Cloutier

Lawrence²,

Goody³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.Aganirsen, an antisense oligonucleotide inhibiting insulin receptor substrate (IRS)-1 expression, has been shown to promote the regression of pathologic corneal neovascularization in patients. In this study, the authors aimed to demonstrate the antiangiogenic activity of aganirsen in animal models of retinal neovascularization. METHODS. Eyedrops of aganirsen were applied daily in nonhuman primates after laser-induced choroidal neovascularization (CNV; model of wet age-related macular degeneration [AMD]) and in newborn rats after oxygen-induced retinopathy (OIR; model of ischemic retinopathy). Retinal aganirsen concentrations were assessed in rabbits and monkeys after topical delivery (21.5, 43, or 86 g). Clinical significance was further evaluated by determination of IRS-1 expression in monkey and human retinal biopsy specimens. RESULTS. Topical corneal application of aganirsen attenuated neovascular lesion development dose dependently in African green monkeys. The incidence of high-grade CNV lesions (grade IV) decreased from 20.5% in vehicle-treated animals to 1.7% (P Ͻ 0.05) at the 86-g dose. Topical aganirsen inhibited retinal neovascularization after OIR in rats (P Ͻ 0.05); furthermore, a single intravitreal injection of aganirsen reduced OIR as effectively as ranibizumab, and their effects were additive. Significantly, topical applications of aganirsen did not interfere with physiological retinal vessel development in newborn rats. Retinal delivery after topical administration was confirmed, and retinal expression of IRS-1 was demonstrated to be elevated in patients with subretinal neovascularization and AMD. CONCLUSIONS. Topical application of aganirsen offers a safe and effective therapy for both choroidal and retinal neovascularization without preventing its normal vascularization. Together, these findings support the clinical testing of aganirsen for human retinal neovascular diseases. (Invest Ophthalmol Vis Sci.

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Section: Laser-induced Cnv In Nonhuman Primatesmentioning

confidence: 99%

Section: Laser-induced Cnv In Nonhuman Primatesmentioning

confidence: 99%

Section: Fluorescein Angiography Scoringmentioning

confidence: 99%

Section: Imagej Analysis Of Angiograms and Oct Imagesmentioning

confidence: 99%

Section: Aganirsen Reduces Pathologic Neovascularization In a Primatementioning

confidence: 99%

See 3 more Smart Citations

Antiangiogenic Activity of Aganirsen in Nonhuman Primate and Rodent Models of Retinal Neovascular Disease after Topical Administration

Cloutier

Lawrence²,

Goody³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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Long‐term therapeutic effect in nonhuman primate eye from a single injection of anti‐VEGF controlled release hydrogel

Lin

Wang

et al. 2019

Bioengineering & Transla Med

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Wet age‐related macular degeneration (wet‐AMD) is a leading cause of irreversible blindness. Current treatment of AMD requires monthly intravitreal injection, which is difficult to be implemented in many parts of the world. In recent years, controlled release of anti‐vascular endothelial growth factor (VEGF) therapeutics has attracted intense research interest aiming to reduce the injection frequency to one or two times per year. In this study, we evaluated the in vivo pharmacokinetics and the long‐term therapeutic efficacy of an in situ hydrogel encapsulating an anti‐VEGF antibody in nonhuman primates. We show that after a single injection of anti‐VEGF controlled release hydrogel, a relatively constant concentration of drug can be maintained in the monkey eye for at least 5 months and the dose was sufficient for the treatment of recurrent choroidal neovascularization induced by repeat laser photocoagulation in monkeys. Our result suggested that when formulated into a controlled release formulation, a single dose of anti‐VEGF may be sufficient for a half‐year treatment and controlled release may be a suitable strategy to reduce the injection frequency in the treatment of AMD in human.

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Laser-Induced Choroidal Neovascularization in Rats

Zhao

Xie

Hein

et al. 2021

Methods in Molecular Biology

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Optimization of laser-induced choroidal neovascularization in African green monkeys

Cited by 39 publications

References 24 publications

Antiangiogenic Activity of Aganirsen in Nonhuman Primate and Rodent Models of Retinal Neovascular Disease after Topical Administration

Antiangiogenic Activity of Aganirsen in Nonhuman Primate and Rodent Models of Retinal Neovascular Disease after Topical Administration

Long‐term therapeutic effect in nonhuman primate eye from a single injection of anti‐VEGF controlled release hydrogel

Laser-Induced Choroidal Neovascularization in Rats

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