Effect of a novel octapeptide urokinase fragment, A°6, on experimental choroidal neovascularization in the monkey

Hyoung J. Koh, William R. Freeman, Stanley P. Azen, Christina Flaxel, Laurie D. Labree, Linguen Cheng, Margaret Wills, Terence R. Jones

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

PURPOSE: To evaluate the inhibitory effects of a urokinase-derived octapeptide, A°6, on laser-induced choroidal neovascularization (CNV) in monkeys. METHODS: Twenty female cynomolgus monkeys were randomly grouped into weekly or monthly A°6 treatment groups, each consisting of 10 animals. CNV was induced in both eyes by perimacular laser treatment. In each right eye, a single 22.25-mg A°6 dose (monthly group) or 4 22.25-mg A°6 doses each week (weekly group) were given by intravitreal injections. Each left eye received phosphate buffer on the same schedule. Monkeys were observed for 4 weeks by ophthalmic examinations, color photography, and fluorescein angiography. RESULTS: Weekly treated eyes had a 35% reduction of CNV compared with controls (P = 0.23). In contrast, monthly treated eye had a 71% reduction of CNV compared with controls (P = 0.0009). There was no evidence of toxicity at both clinical and pathologic examinations. CONCLUSIONS: Intravitreal A°6 injections effectively inhibited CNV in cynomolgus monkeys without evidence of toxicity. The overall reduction in CNV was greater for monthly treated eyes than for weekly treated eyes. This study suggests that A°6 has promise as a local antiangiogenic treatment of CNV. Further work is indicated to evaluate the potential role of A°6 in therapy for human CNV associated with age-related macular degeneration.

Original languageEnglish (US)
Pages (from-to)202-209
Number of pages8
JournalRetina
Volume26
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

Fingerprint

Choroidal Neovascularization
Urokinase-Type Plasminogen Activator
Haplorhini
Intravitreal Injections
Macaca fascicularis
Lasers
Eye Color
Fluorescein Angiography
Photography
Macular Degeneration
Therapeutics
Appointments and Schedules
Buffers
Phosphates

Keywords

  • Age-related macular degeneration
  • Angiogenesis
  • Animal model
  • Choroidal neovascularization

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Effect of a novel octapeptide urokinase fragment, A°6, on experimental choroidal neovascularization in the monkey. / Koh, Hyoung J.; Freeman, William R.; Azen, Stanley P.; Flaxel, Christina; Labree, Laurie D.; Cheng, Linguen; Wills, Margaret; Jones, Terence R.

In: Retina, Vol. 26, No. 2, 02.2006, p. 202-209.

Research output: Contribution to journalArticle

Koh, Hyoung J. ; Freeman, William R. ; Azen, Stanley P. ; Flaxel, Christina ; Labree, Laurie D. ; Cheng, Linguen ; Wills, Margaret ; Jones, Terence R. / Effect of a novel octapeptide urokinase fragment, A°6, on experimental choroidal neovascularization in the monkey. In: Retina. 2006 ; Vol. 26, No. 2. pp. 202-209.
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abstract = "PURPOSE: To evaluate the inhibitory effects of a urokinase-derived octapeptide, A°6, on laser-induced choroidal neovascularization (CNV) in monkeys. METHODS: Twenty female cynomolgus monkeys were randomly grouped into weekly or monthly A°6 treatment groups, each consisting of 10 animals. CNV was induced in both eyes by perimacular laser treatment. In each right eye, a single 22.25-mg A°6 dose (monthly group) or 4 22.25-mg A°6 doses each week (weekly group) were given by intravitreal injections. Each left eye received phosphate buffer on the same schedule. Monkeys were observed for 4 weeks by ophthalmic examinations, color photography, and fluorescein angiography. RESULTS: Weekly treated eyes had a 35{\%} reduction of CNV compared with controls (P = 0.23). In contrast, monthly treated eye had a 71{\%} reduction of CNV compared with controls (P = 0.0009). There was no evidence of toxicity at both clinical and pathologic examinations. CONCLUSIONS: Intravitreal A°6 injections effectively inhibited CNV in cynomolgus monkeys without evidence of toxicity. The overall reduction in CNV was greater for monthly treated eyes than for weekly treated eyes. This study suggests that A°6 has promise as a local antiangiogenic treatment of CNV. Further work is indicated to evaluate the potential role of A°6 in therapy for human CNV associated with age-related macular degeneration.",
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T1 - Effect of a novel octapeptide urokinase fragment, A°6, on experimental choroidal neovascularization in the monkey

AU - Koh, Hyoung J.

AU - Freeman, William R.

AU - Azen, Stanley P.

AU - Flaxel, Christina

AU - Labree, Laurie D.

AU - Cheng, Linguen

AU - Wills, Margaret

AU - Jones, Terence R.

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N2 - PURPOSE: To evaluate the inhibitory effects of a urokinase-derived octapeptide, A°6, on laser-induced choroidal neovascularization (CNV) in monkeys. METHODS: Twenty female cynomolgus monkeys were randomly grouped into weekly or monthly A°6 treatment groups, each consisting of 10 animals. CNV was induced in both eyes by perimacular laser treatment. In each right eye, a single 22.25-mg A°6 dose (monthly group) or 4 22.25-mg A°6 doses each week (weekly group) were given by intravitreal injections. Each left eye received phosphate buffer on the same schedule. Monkeys were observed for 4 weeks by ophthalmic examinations, color photography, and fluorescein angiography. RESULTS: Weekly treated eyes had a 35% reduction of CNV compared with controls (P = 0.23). In contrast, monthly treated eye had a 71% reduction of CNV compared with controls (P = 0.0009). There was no evidence of toxicity at both clinical and pathologic examinations. CONCLUSIONS: Intravitreal A°6 injections effectively inhibited CNV in cynomolgus monkeys without evidence of toxicity. The overall reduction in CNV was greater for monthly treated eyes than for weekly treated eyes. This study suggests that A°6 has promise as a local antiangiogenic treatment of CNV. Further work is indicated to evaluate the potential role of A°6 in therapy for human CNV associated with age-related macular degeneration.

AB - PURPOSE: To evaluate the inhibitory effects of a urokinase-derived octapeptide, A°6, on laser-induced choroidal neovascularization (CNV) in monkeys. METHODS: Twenty female cynomolgus monkeys were randomly grouped into weekly or monthly A°6 treatment groups, each consisting of 10 animals. CNV was induced in both eyes by perimacular laser treatment. In each right eye, a single 22.25-mg A°6 dose (monthly group) or 4 22.25-mg A°6 doses each week (weekly group) were given by intravitreal injections. Each left eye received phosphate buffer on the same schedule. Monkeys were observed for 4 weeks by ophthalmic examinations, color photography, and fluorescein angiography. RESULTS: Weekly treated eyes had a 35% reduction of CNV compared with controls (P = 0.23). In contrast, monthly treated eye had a 71% reduction of CNV compared with controls (P = 0.0009). There was no evidence of toxicity at both clinical and pathologic examinations. CONCLUSIONS: Intravitreal A°6 injections effectively inhibited CNV in cynomolgus monkeys without evidence of toxicity. The overall reduction in CNV was greater for monthly treated eyes than for weekly treated eyes. This study suggests that A°6 has promise as a local antiangiogenic treatment of CNV. Further work is indicated to evaluate the potential role of A°6 in therapy for human CNV associated with age-related macular degeneration.

KW - Age-related macular degeneration

KW - Angiogenesis

KW - Animal model

KW - Choroidal neovascularization

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