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Y. Lei, B. Caterson, D. Tudor, M. E. Boulton, M. P. Fautsch, M. R. Hernandez, J. E. Morgan; The Expression of Chondroitin Sulphate Glycosaminoglycans and Aggrecan Core Protein Epitopes in Young, Aged, and Glaucomatous Human Retinas. Invest. Ophthalmol. Vis. Sci. 2008;49(13):761.
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© ARVO (1962-2015); The Authors (2016-present)
The perineuronal net is one of the major hurdles which prevent neurons from regenerating and remodelling. To determine its importance in the repair of visual pathways, we compared the expression of chondroitin sulphate- glycosaminoglycans (CS-GAGs) and aggrecan core protein epitopes in young, aged and glaucomatous retinas.
12 human retinas were used in the study: young (18-33 yr, n=4), aged (60-85 yr, n=4) and glaucoma (67-89 yr, n=4). Retinal transverse sections were labelled using a range of monoclonal antibodies (mAbs) against CS-GAGs, keratan sulphated-GAGs (KS-GAGs), and aggrecan, decorin, biglycan, lumican, keratocan and versican core proteins, and analysed by immunohistochemistry.
CS-GAGs (0-, 4- & 6-sulphated) were detected as chondroitinase generated 'CS-stubs' using mAbs 1B5, 2B6 & 3B3 respectively, and aggrecan core protein using mAbs 6B4 and 7D1. All of these were expressed in three groups of retinas; the expression of 2B6 and 6B4 appeared to be up-regulated in the glaucoma group. Because only negative staining for decorin, biglycan, lumican, keratocan and versican was found, the major source of CS-GAG staining appears to be from aggrecan. Also, negative 5D4 staining suggests that this aggrecan in the retina is not or minimally substituted with KS-GAGs. In the interphotoreceptor matrix, the staining of CS-GAGs was co-localised with aggrecan core protein. Additionally, 6B4 and 7D1 were expressed in the inner retina, including the inner nucleus layers (INL), the inner plexiform layer (IPL), and the retinal ganglion cell layer (RGCL). This indicates that aggrecan core protein is expressed in these retinal tissue domains.
This is the first report showing the difference between CS-GAG staining and aggrecan core protein staining in the human retina. It suggests that in the INL, IPL and RGCL the GAG attachment regions of aggrecan have been removed. The perineuronal net may inhibit the adult human retina from recovery following injury via their CS chains and/or aggrecan core protein.
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