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Matthew Nguyen, Michelle Lajko, William Chang, Amani A Fawzi; Biomolecular Markers of Angiogenesis in Proliferative Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5425.
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© ARVO (1962-2015); The Authors (2016-present)
In late stage diabetic retinopathy, a phenomenon known as proliferative diabetic retinopathy (PDR) occurs, where growth factors secreted by the retina leads to epiretinal proliferation of fibrovascular membranes (FVM), and subsequently, the development of traction detachments. The exact molecular mechanisms of this process remain unclear. We utilized immunohistochemical methods to identify specific molecular markers that may better elucidate the angiogenic mechanisms in FVM and compared them to idiopathic epiretinal membranes (ERMs).
ERMs and FVMs were obtained from patients undergoing pars plana vitrectomy, and were designated as either PDR-related or idiopathic based on the patient’s indication for vitrectomy. All collected membranes were cryo-protected, fixed in paraformaldehyde, and cryo-sectioned. The sectioned membranes were stained with hypoxia-inducible factor 1, alpha subunit (HIF-1a), platelet-derived growth factor (PDGF-BB), and fibroblast-specific protein 1 (FSP-1), all being factors that influence angiogenesis under hypoxic conditions in tumor models.
HIF-1a immunoreactivity was seen mainly in the cytoplasm of cells in both FVM and idiopathic ERMs, with qualitative imaging that suggests increased immunoreactivity in FVMs. PDGF and FSP-1 immunoreactivities followed similar patterns, suggesting a correlative influence between HIF-1a and its downstream influence on PDGF and FSP-1. We are currently quantifying these markers using confocal microscopy imaging and quantitative software analysis.
Hypoxic conditions influences angiogenesis through HIF-1a and its downstream effect on PDGF, possibly involving the same mechanisms shown in previous tumor models such as attracting pericytes and smooth muscle cells. HIF-1a also seems to upregulate FSP-1, a fibroblast-specific marker that has been implicated in angiogenesis in cancer cell metastasis; however the increased immunoreactivity of FSP-1 in FVM compared to ERM suggests a greater role for this marker in FVM membrane formation and angiogenesis. This research may further elucidate the specific pathways and mechanisms through which these angiogenic markers are implicated in PDR and thus may provide potential targets for therapeutic intervention.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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