Inhibition of pathologic retinal neovascularization by a small peptide derived from human apolipoprotein(a).
OBJECTIVE
To evaluate the effect of KV11, a novel 11-mer peptide from human apolipoprotein(a), against retinal neovascularization and to study its penetration and the possible toxicity to the retina.


METHODS
Wound-healing, a modified Boyden chamber, and MTS assays were used to evaluate the effect of KV11 on the migration and proliferation of bovine retinal capillary endothelial cells (BRCECs) induced by vascular endothelial growth factor (VEGF) in vitro. The antiangiogenic effect of KV11 was also studied with a mouse model of oxygen-induced retinopathy. Then, FITC-labeled KV11 was injected into the vitreous of normal rabbits, the retinal penetration was determined by confocal laser-scanning microscope, and further confirmed by UPLC/MS analysis of KV11 in tissue extracts. Electrophysiological tests and histologic examinations were used to study the possible toxicity of KV11 against rabbit neuroretina after intravitreal administration.


RESULTS
KV11 inhibited VEGF-induced BRCEC migration but not proliferation and reduced the pathologic neovascularization in a mouse model, without affecting normal retinal vasculature. FITC-labeled KV11 appeared in the retina within 30 minutes after injection and diffused to all layers 3 hours later. The transfer of KV11 from the vitreous to the retina was confirmed by UPLC/MS data. Electrophysiologic tests and histologic examinations revealed no evident functional or morphologic abnormalities in rabbit neuroretina after KV11 injection.


CONCLUSIONS
It is concluded that the novel peptide KV11 is an effective inhibitor of retinal pathologic angiogenesis with a sufficient retinal penetration and a favorable safety profile and may provide a promising alternative for ocular antiangiogenic therapy.
Zhao
Hui
H
Department of Ophthalmology, First People's Hospital, Shanghai JiaoTong University, Shanghai, China.
Jin
Huiyi
H
Li
Qian
Q
Gu
Qing
Q
Zheng
Zhi
Z
Wu
Haixiang
H
Ye
Siwei
S
Sun
Xiaodong
X
Xu
Xun
X
Ho
Patrick C P
PC
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001054:Apolipoproteins A / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D007267:Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010100:Oxygen / Q000633:toxicity; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D012171:Retinal Vessels / Q000166:cytology; D014822:Vitreous Body / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D001054:Apolipoproteins A; C534296:KV11 peptide, human; D010446:Peptide Fragments; D010100:Oxygen