Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration

• Published in: Experimental eye research 2006-01, Vol.82 (1), p.99-110
• Main Authors: Bhutto, Imran A., McLeod, D. Scott, Hasegawa, Takuya, Kim, Sahng Y., Merges, Carol, Tong, Patrick, Lutty, Gerard A.
• Format: Article
• Language: English
• Subjects: age-related macular degeneration; Aged; Aged, 80 and over; Bruch Membrane - chemistry; Bruch's membrane; Case-Control Studies; choroid; Choroid - chemistry; choroidal neovascularization; Choroidal Neovascularization - metabolism; Eye Proteins - analysis; Female; Humans; Immunohistochemistry - methods; Macular Degeneration - metabolism; Male; Middle Aged; Nerve Growth Factors - analysis; Pigment Epithelium of Eye - chemistry; pigment epithelium-derived factor; RPE; Serpins - analysis; vascular endothelial growth factor; Vascular Endothelial Growth Factor A - analysis
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2005.05.007

The purpose of this study was to examine the localization and relative levels of vascular endothelial growth factor (VEGF; an angiogenic factor) and pigment epithelium-derived factor (PEDF; an antiangiogenic factor) in aged human choroid and to determine if the localization or their relative levels changed in age-related macular degeneration (AMD). Ocular tissues were obtained from eight aged control donors (age range, 75–86 years; mean age, 79.8 years) with no evidence or history of chorioretinal disease and from 12 donors diagnosed with AMD (age range, 61–105 years; mean age, 83.9 years). Tissues were cryopreserved and streptavidin alkaline phosphatase immunohistochemistry was performed with rabbit polyclonal anti-human VEGF and rabbit polyclonal anti-human PEDF antibodies. Binding of the antibodies was blocked by preincubation of the antibody with an excess of recombinant human PEDF or VEGF peptide. Choroidal blood vessels were identified with mouse anti-human CD-34 antibody in adjacent tissue sections. Three independent observers graded the immunohistochemical reaction product. The most prominent sites of VEGF and PEDF localization in aged control choroid were RPE–Bruch's membrane–choriocapillaris complex including RPE basal lamina, intercapillary septa, and choroidal stroma. There was no significant difference in immunostaining intensity and localization of VEGF and PEDF in aged control choroids. The most intense VEGF immunoreactivity was observed in leukocytes within blood vessels. AMD choroid had a similar pattern and intensity of VEGF immunostaining to that observed in aged controls. However, PEDF immunoreactivity was significantly lower in RPE cells ( p=0.0073), RPE basal lamina ( p=0.0141), Bruch's membrane ( p