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. 2009 Jul;33(7):765-71.
doi: 10.1016/j.cellbi.2009.04.013. Epub 2009 May 5.

Inhibition of new vessel growth in mouse model of laser-induced choroidal neovascularization by adiponectin peptide II

Valeriy V Lyzogubov  1 , Ruslana G Tytarenko, Sushma Thotakura, Tito Viswanathan, Nalini S Bora, Puran S Bora
Affiliations

Inhibition of new vessel growth in mouse model of laser-induced choroidal neovascularization by adiponectin peptide II

Valeriy V Lyzogubov et al. Cell Biol Int. 2009 Jul.

Abstract

We have investigated the effect of adiponectin (APN) peptide II on new vessel growth in mouse model of choroidal neovascularization (CNV) or wet type age-related macular degeneration (AMD). Mice were injected intraperitoneally with APN peptide II, control peptide, or PBS on day 1-7 or day 5-14. APN, AdipoR1, PCNA, and VEGF localization was investigated using confocal microscopy, immunohistochemistry, and RT-PCR. APN peptide II decreased the relative area of FITC-dextran perfused vessels by 4-fold, PCNA expression by 3-fold, and the number of PCNA stained HUVEC and MAVEC cells by 38 and 46%, respectively. We concluded that APN peptide II inhibits CNV size on days 7 and 14 by inhibiting the proliferation of endothelial cells in vivo and in vitro. APN peptide II may have therapeutic potential to inhibit CNV or wet AMD.

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Figures

Fig. 1
Fig. 1
Immunohistochemical co-localization of APN (A, red) and AdipoR1 (B, green) in a choroid vessel (v). Sites of APN and adipoR1 co-localization (C, yellow) were close to the apical surface of endothelial cells (arrow). Nuclei were stained with DAPI (blue color).
Fig. 2
Fig. 2
Confocal micrographs of mouse RPE-choroid-sclera flat mounts. Treatment with APN peptide II or control solutions was performed from day 1 to day 7 after laser. CNV (green color) size in PBS (A) and control peptide-treated mice (B) was larger compared to APN peptide II-treated animals (C). APN peptide II significantly decreased relative area of CNV (D). Number of spots in each group was 20. *p < 0.05 compared to PBS-treated control; #p < 0.05 compared to control peptide treated.
Fig. 3
Fig. 3
Confocal micrographs of mouse RPE-choroid-sclera flat mounts. Treatment with APN peptide II or control solution was performed from day 5 to day 14 after laser. CNV (green color) size in control peptide-treated mice (A) treated mice was larger compared to APN peptide II-treated animals (B). APN peptide II significantly decreased relative area of CNV (C). Number of spots in each group was 20. *p < 0.05 compared to control peptide-treated.
Fig. 4
Fig. 4
Three-dimensional structures of control peptide (A) and APN peptide II (B). Lowest energy conformer of the polypeptides obtained using the SYBYL program. The possible binding site of APN peptide II to receptor is marked in circle.
Fig. 5
Fig. 5
Expression of VEGF in mouse choroid. Total RNA was extracted from the RPE-choroid tissue. PCR products were analyzed on a 1% agarose gel (A). APN peptide II decreased VEGF RNA expression on day 3 after laser. Line 1, control; line 2, APN peptide II (B). Formalin fixed, paraffin embedded section were IHC stained for VEGF. Expression of VEGF (purple color) was significantly lower in choroid of APN peptide II-treated animals (C) compared to control (D).
Fig. 6
Fig. 6
Quantitative immunohistochemical analysis of APN peptide II on PCNA expression in the area of laser injury. Isolectin IB4 positive cells (red color) located in choroid (Ch) and subretinal tissue (SRT) of both groups. PCNA positive green stained nuclei were more numerous in CNV area of control peptide (A), compared to APN peptide II-treated animals (B). APN peptide II significantly decreased (4%) PCNA positive nuclei in the area of laser injury on day 7 compared to control peptide (12%) (C). The numbers of spots investigated per group were 21. *p < 0.05.
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