Inhibitory role of adiponectin peptide I on rat choroidal neovascularization.
Age-related macular degeneration (AMD) is a leading cause of central blindness in the elderly population. The wet type of AMD is characterized by extensive growth of new vessels. One of the effective strategies to treat wet AMD is to limit the choroidal neovascularization (CNV). We studied the effects of adiponectin peptide I (APNpI) on new vessel growth in laser-induced rat model of wet AMD and on rat choroidal endothelial cell (CEC) culture. CNV size and vessel density were investigated by microscopy. Immunohistochemical staining (IHC) for von Willebrand Factor (vWF), APN, APN receptors 1 (AdipoR1), 2 (AdipoR2), VEGF, VEGF receptor 2 (VEGF-R2), proliferating cell nuclear antigen (PCNA) was performed in CNV area. The mRNA expression of VEGF and VEGF-R2 in RPE-choroid was investigated by RT-PCR and real-time PCR. APNpI inhibited area of CNV by 4 fold, number of vWF positive vessels by 99% and area of subretinal tissue by 40%. The expression of VEGF and VEGF-R2 at mRNA and protein levels decreased after APNpI treatment in vivo. Proliferative index (PCNA) was 5 folds less in laser spots of APNpI treated rats compared to controls. In conclusion, APNpI inhibited formation of new vessels in rat model of CNV by decreasing VEGF, VEGF-R2 expression and cell proliferation. Thus, APNpI may have potential therapeutic use for AMD treatment since it significantly inhibited CNV.
Department of Ophthalmology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Valeriy V
VV
Lyzogubov
Ruslana G
RG
Tytarenko
Nalini S
NS
Bora
Puran S
PS
Bora
D052242:Adiponectin / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002829:Choroid / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D020256:Choroidal Neovascularization / Q000517:prevention & control*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011914:Rats, Inbred BN; D054419:Receptors, Adiponectin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D057135:Wet Macular Degeneration / Q000188:drug therapy*
D052242:Adiponectin; D010446:Peptide Fragments; D018809:Proliferating Cell Nuclear Antigen; D054419:Receptors, Adiponectin; D042461:Vascular Endothelial Growth Factor A; C504339:adiponectin receptor 1, rat; C506573:adiponectin receptor 2, rat; C467498:vascular endothelial growth factor A, rat; D040301:Vascular Endothelial Growth Factor Receptor-2