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C.K. Spee, J. Wu, R. Kannan, S.J. Ryan, D.R. Hinton; Patterns of Expression of Bone Morphogenic Protein–4 (BMP–4) in Age–Related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2006;47(13):867.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the pattern of expression of BMP–4 in the retina/choroid from patients with age related macular degeneration (AMD).
Eyes from normal donors and confirmed cases of AMD were obtained from the Lions Eye Bank of Oregon and the Lions Doheny Eye Bank in Los Angeles. All samples were obtained within 36 hours post mortem. The cornea, lens and vitreous were carefully removed and the macula of the OD and OS eyes were carefully dissected out and frozen in OCT freezing media. The retina was removed from several regions of the macula to expose areas of drusen when present, and areas without drusen and similarly frozen. Thick sections (8µm) were cut on a cryostat and the sections were immunohistochemically stained with a polyclonal BMP–4 antibody (Santa Cruz Biotechnology).
No apparent expression of BMP–4 could be found in retinal pigment epithelial cells (RPE) and choroid of normal human donor frozen sections (12 donors, ages 25–90) by immunohistochemical analysis. In contrast, RPE/Choroid samples from 8/10 patients with pathologically diagnosed early AMD showed prominent expression of BMP–4 protein in RPE and in the vicinity of Bruch’s membrane adjacent to hard and soft drusen. In 3/3 samples with geographic atrophy, BMP–4 expression was prominent in the RPE and thickened Bruch’s membrane adjacent to areas of RPE loss, and was associated with the choroidal vasculature. In contrast, BMP–4 expression was not seen in RPE or neovascular tissue from any of the 12 surgically excised choroidal neovascular (CNV) membranes from patients with AMD. Two patients were identified in whom subretinal scar tissue was found adjacent to areas of geographic atrophy. Focal strong BMP–4 staining was seen in RPE at the periphery of the subretinal scars.
Our findings suggest that BMP–4 signaling may be playing a role in the switch between senescence and cell death found in geographic atrophy, or proliferation of endothelial cells found in CNV. The mechanisms and pathways of signaling need to be elucidated.
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