Expression of pigment epithelium-derived factor in experimental choroidal neovascularization.

Angiogenesis Laboratory, Retina Research Institute, Massachusetts Eye and Ear Infirmary, 245 Charles Street, Boston, MA 02114, USA.
Investigative Ophthalmology &amp Visual Science (Impact Factor: 3.66). 06/2002; 43(5):1574-80.
Source: PubMed

ABSTRACT To investigate the expression of pigment epithelium-derived factor (PEDF) in the rat laser-injury model of choroidal neovascularization (CNV).
Retinas were immunostained for PEDF at different times (1, 2, and 3 weeks) after laser injury. Levels of PEDF protein in the vitreous at 1, 3, 7, 14, and 28 days after laser injury were also assayed by Western blot.
Protein levels of PEDF in the vitreous were increased during the first 7 days after CNV induction. Immunostaining for PEDF was observed throughout normal nonlasered control retinas, sham-lasered retinas, and areas remote to laser lesions, which were generally more intense in the outer nuclear layer (ONL) and less intense in the internal nuclear layer (INL). Decreased expression of PEDF was observed in flanking areas adjacent to the injury site and was confined mainly to the ONL. In the injury sites, immunostaining within the ONL was either absent or decreased for up to 3 weeks after laser injury (the duration of the study). Preadsorption of the anti-PEDF antibody with the immunizing peptide blocked specific labeling in the retina.
These results demonstrate an inverse correlation of expression of PEDF and formation of CNV in the experimental model and suggest that decreased expression of PEDF plays a permissive role in the formation of CNV. PEDF analogues may be a reasonable treatment strategy for CNV.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Retinal ischemia/reperfusion (I/R) injury is an important cause of visual impairment. However, questions remain on the overall I/R mechanisms responsible for progressive damage to the retina. In this study, we used a mouse model of I/R and characterized the pathogenesis by analyzing temporal changes of retinal morphology and function associated with changes in retinal gene expression. Transient ischemia was induced in one eye of C57BL/6 mice by raising intraocular pressure to 120 mmHg for 60 min followed by retinal reperfusion by restoring normal pressure. At various time points post I/R, retinal changes were monitored by histological assessment with H&E staining and by SD-OCT scanning. Retinal function was also measured by scotopic ERG. Temporal changes in retinal gene expression were analyzed using cDNA microarrays and real-time RT-PCR. In addition, retinal ganglion cells and gliosis were observed by immunohistochemistry. H&E staining and SD-OCT scanning showed an initial increase followed by a significant reduction of retinal thickness in I/R eyes accompanied with cell loss compared to contralateral control eyes. The greatest reduction in thickness was in the inner plexiform layer (IPL) and inner nuclear layer (INL). Retinal detachment was observed at days 3 and 7 post- I/R injury. Scotopic ERG a- and b-wave amplitudes and implicit times were significantly impaired in I/R eyes compared to contralateral control eyes. Microarray data showed temporal changes in gene expression involving various gene clusters such as molecular chaperones and inflammation. Furthermore, immunohistochemical staining confirmed Muller cell gliosis in the damaged retinas. The time-dependent changes in retinal morphology were significantly associated with functional impairment and altered retinal gene expression. We demonstrated that I/R-mediated morphological changes the retina closely associated with functional impairment as well as temporal changes in retinal gene expression. Our findings will provide further understanding of molecular pathogenesis associated with ischemic injury to the retina.
    Molecular Neurodegeneration 06/2013; 8(1):21. DOI:10.1186/1750-1326-8-21 · 5.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study is to evaluate the effects of docosahexaenoic acid (DHA), a major omega-3-polyunsaturated fatty acid (ω-3-PUFAs), in the development of experimental choroidal neovascularization (CNV) in rodents. Experimental second generation Long Evans rats fed with diets of varying ω-3-PUFA content designed to produce significantly different retinal DHA levels were used in our studies. A transgenic mouse model (fat-1) engineered to over-produce DHA was also studied. CNV was induced by rupture of Bruch's membrane using laser photocoagulation. At 7 days after induction, animals were euthanatized, and eyes were collected. RPE/choroid flatmounts were labeled with isolectin IB4 to determine CNV lesion volumes using confocal microscopy and high-performance 3D imaging software. The median of CNV complex volumes of animals with DHA-adequate diets was lower by 63% relative to that of animals with DHA-deficient diets. The median of CNV complex volumes in fat-1 transgenic mice was decreased by 59% relative to that of wild type controls. Dietary intake or genetic manipulation to increase the sources of DHA significantly diminished the volume of induced CNV lesions in rodents. They suggest that consumption of ω-3-PUFAs may serve to prevent CNV.
    10/2011; 2. DOI:10.4172/2155-9570.1000187
  • [Show abstract] [Hide abstract]
    ABSTRACT: Vasohibin-1 has been recently detected in endothelial cells and identified as a negative feedback regulator of angiogenesis induced by VEGF-A. However, the expression of Vasohibin-1 in colorectal cancer and its correlations with VEGF-A, microvessel density (MVD), and the prognosis of the patients remain unclear. In this study, Vasohibin-1 and VEGF-A expression were measured in 132 paraffin-embedded tissues of colorectal cancer by immunohistochemistry and Western blot, as well as in colon cancer cell lines with different metastatic potential and in normal colon cell by Western blot and real-time PCR. MVD was measured by counting CD34 positive clusters in a single field of view with the most intensive neovascularization of colon cancer tissues. The correlation between the expression of Vasohibin-1, VEGF-A, MVD, clinicopathological features, and prognosis was analyzed. We found that Vasohibin-1 and VEGF-A proteins were expressed in 88.64 % (117/132) and 84.09 % (111/132) colorectal cancer tissues, respectively. Strongly positive correlations were found between Vasohibin-1, VEGF-A expression, and MVD in the colorectal cancer tissues (Vasohibin-1 vs. r = 0.688, P < 0.001; Vasohibin-1 vs. MVD: r = 0.483, P < 0.001; VEGF-A vs. MVD: r = 0.491, P < 0.001). Vasohibin-1 expression has significant positive correlation with pathological TNM stage (P = 0.001), tumor stromal invasion (P = 0.004), lymph node status (P = 0.003), and distant metastasis (P = 0.033), but no correlation with tumor differentiation (P = 0.756). The patients with high Vasohibin-1 expression had significantly worse overall survival (OS) and progression-free survival (PFS) than those with low Vasohibin-1 expression (OS: P = 0.001; PFS: P = 0.003). In addition, Vasohibin-1 protein expression is an independent risk factor affecting OS and PFS. Therefore, we conclude that Vasohibin-1 is a clinically relevant predictor of patient prognosis in colorectal cancer. Vasohibin-1 might become a new biomarker and provide additional prognostic information in patients with colorectal cancer.
    Medical Oncology 02/2014; 31(2):816. DOI:10.1007/s12032-013-0816-0 · 2.06 Impact Factor


Available from