Therapeutic Efficacy of a Novel Acetylated Tetrapeptide in Animal Models of Age-Related Macular Degeneration

It has been shown previously that a novel tetrapeptide, Arg-Leu-Tyr-Glu (RLYE), derived from human plasminogen inhibits vascular endothelial growth factor (VEGF)-induced angiogenesis, suppresses choroidal neovascularization in mice by an inhibition of VEGF receptor-2 (VEGFR-2) specific signaling pat...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-04, Vol.22 (8), p.3893
Main Authors: Koo, Hye Cheong, Baek, Yi-Yong, Choi, Jun-Sup, Kim, Young-Myeong, Sung, Bokyung, Kim, Min-Jung, Kim, Jae Gyu, You, Ji Chang
Format: Article
Language:English
Subjects:
acetylated tetrapeptide (Ac-RLYE)
Angiogenesis
Animal models
Animals
Antibodies
Cataracts
Degenerative diseases
Diabetes
Diabetic retinopathy
Dosage
Drug dosages
Growth factors
In vivo methods and tests
laser-induced CNV model
Lasers
Macular degeneration
neovascular age-related macular degeneration
Peptides
Pharmacokinetics
Rabbits
resistance
Retina
Retinal degeneration
retinal neovascularization
Signal transduction
Vascular endothelial growth factor
Vascular endothelial growth factor receptors
Vascularization
VEGF
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Summary:It has been shown previously that a novel tetrapeptide, Arg-Leu-Tyr-Glu (RLYE), derived from human plasminogen inhibits vascular endothelial growth factor (VEGF)-induced angiogenesis, suppresses choroidal neovascularization in mice by an inhibition of VEGF receptor-2 (VEGFR-2) specific signaling pathway. In this study, we report that a modified tetrapeptide (Ac-RLYE) showed improved anti-choroidal neovascularization (CNV) efficacy in a number of animal models of neovascular age-related macular degeneration (AMD) which include rat, rabbit, and minipig. The preventive and therapeutic in vivo efficacy of Ac-RLYE via following intravitreal administration was determined to be either similar or superior to that of ranibizumab and aflibercept. Assessment of the intraocular pharmacokinetic and toxicokinetic properties of Ac-RLYE in rabbits demonstrated that it rapidly reached the retina with minimal systemic exposure after a single intravitreal dose, and it did not accumulate in plasma during repetitive dosing (bi-weekly for 14 weeks). Our results suggested that Ac-RLYE has a great potential for an alternative therapeutics for neovascular (wet) AMD. Since the amino acids in human VEGFR-2 targeted by Ac-RLYE are conserved among the animals employed in this study, the therapeutic efficacies of Ac-RLYE evaluated in those animals are predicted to be observed in human patients suffering from retinal degenerative diseases.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22083893