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J. A. Fuller, A.-M. Brun-Zinkernagel, A. F. Clark, R. J. Wordinger; Differential Expression of Proprotein Convertase PACE4 in the Retina and Optic Nerve Head. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3267.
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The proprotein convertases (PC) are a family of subtilisin/kexin-like serine proteases that are known to process a wide variety of proteins into active forms. Recent studies have suggested that PC modulation may be involved in many conditions including tumor invasiveness and nervous system damage. PACE4 regulation has been demonstrated to modulate the bioavailability of transforming growth factor (TGF) related proteins. The purpose of this study is to determine the expression patterns for PACE4 in the human retina and optic nerve head.
RNA was isolated from postmortem human brain, retina, and optic nerve head, and mRNA expression levels for members of the PC family were determined using Quantitative real-time polymerase chain reaction (QRT-PCR). Protein lysaets generated from postmortem human retina and optic nerve were analyzed for PACE4 expression via immunoblotting. Immunohistochemistry was used to localize the PC family in the retina and optic nerve head.
Immunohistochemistry for PC1 demonstrates strong staining throughout the retina, with decreased expression in GFAP positive cells in the ganglion cell layer/nerve fiber layer. PC1 mRNA expression is highest in postmortem brain, and 1.5 fold lower in ONH relative to retina. PC2 expression is highest in retina, and is approximately 4.5 fold lower in ONH relative to retina. Furin and PC7 mRNA levels are not significantly different between retina and ONH, but both demonstrate higher expression compared to postmortem brain. PACE4 mRNA expression is 1.7 and 2.5 fold higher in postmortem human ONH relative to postmortem retina and brain, respectively. Immunoblotting for PACE4 demonstrates prominent bands at approx 70 and 44 kDa in retina and optic nerve lysates.
This study suggests that PACE4 may be an important regulator in the processing and maturation of growth factors in the optic nerve head, and may be an upstream mediator of gliosis and extracellular matrix remodeling of the ONH in primary open angle glaucoma (POAG).
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