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Sebastian Funke, Natarajan Perumal, Sabine Beck, Silke Gabel-Scheurich, Carsten Schmelter, Claudia Gerbig, Oliver Gramlich, Norbert Pfeiffer, Franz H Grus; Mass Spectrometric Proteomic Analysis of Human Glaucomatous Retinae. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3658.
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© ARVO (1962-2015); The Authors (2016-present)
Proteomic changes have been observed due to neurodegenerative processes in ocular sample species, in cell and animal models. Investigations on human retina samples are still rare. Therefore, we analyzed retina samples of glaucoma and non-glaucoma control donors by mass spectrometry (MS) to uncover glaucoma associated proteomic changes and to provide new molecular candidates contributing to a better understanding of glaucoma.
Retina extracts of glaucoma donors (N=5) and non-glaucoma donors (N=5) have been analyzed using a bottom-up high performance liquid chromatography electro spray ionization MS (BU HPLC ESI MS) workflow followed by label-free quantification and functional analysis. Candidate protein validation has been realized in pooled samples using targeted label-free quantification. Candidates have been verified in the retinal ganglion cell layer (GCL) by laser capture microdissection (LCM).
BU HPLC ESI MS of human retina samples resulted in the identification of >600 proteins (FDR<1%). 10% of proteins showed distinct alterations related to glaucoma. Among these proteins, especially mitochondrial and nucleus species, displayed significant or distinct glaucoma associated level alterations (p<0.05, p<0.1). Abundance changes of key process participants of cell death or cell development could be recorded. Beyond increase of stress related proteins, also decrease of new glaucoma related candidates encircling GCL supported ADP/ATP translocase 3 (ANT3) and methyl-CpG-binding protein 2 (MeCp2) could be documented.
A sensitive view to the human retina proteome could be achieved. Moreover, distinct proteomic changes affecting key cellular processes could be revealed in human glaucoma retinae recommending new candidate proteins, e.g. ANT3 and MeCp2.
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