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- Title
Anti-neurotrophic effects from autoantibodies in adult diabetes having primary open angle glaucoma or dementia.
- Authors
Zimering, Mark B.; Moritz, Thomas E.; Donnelly, Robert J.
- Abstract
Aim: To test for anti-endothelial and anti-neurotrophic effects from autoantibodies in sub-sets of diabetes having open-angle glaucoma, dementia, or control subjects. Methods: Protein-A eluates from plasma of 20 diabetic subjects having glaucoma or suspects and 34 age-matched controls were tested for effects on neurite outgrowth in rat pheochromocytoma PC12 cells or endothelial cell survival. The mechanism of the diabetic glaucoma autoantibodies' neurite-inhibitory effect was investigated in co-incubations with the selective Rho kinase inhibitor Y27632 or the sulfated proteoglycan synthesis inhibitor sodium chlorate. Stored protein-A eluates from certain diabetic glaucoma or dementia subjects which contained long-lasting, highly stable cell inhibitory substances were characterized using mass spectrometry and amino acid sequencing. Results: Diabetic primary open angle glaucoma (POAG) or suspects (n =20) or diabetic dementia (n=3) autoantibodies caused significantly greater mean inhibition of neurite out-growth in PC12 cells (p <0.0001) compared to autoantibodies in control diabetic (n =24) or non-diabetic (n=10) subjects without glaucoma (p <0.01). Neurite inhibition by the diabetic glaucoma autoantibodies was completely abolished by 10μM concentrations of Y27632 (n=4). It was substantially reduced by 30mM concentrations of sodium chlorate (n=4). Peak, long-lasting activity survived storage ×5 years at 0-4°C and was associated with a restricted subtype of Ig kappa light chain. Diabetic glaucoma or dementia autoantibodies (n=5) caused contraction and process retraction in quiescent cerebral cortical astrocytes effects which were blocked by 5μM concentrations of Y27632. Conclusion: These data suggest that autoantibodies in subsets of adult diabetes having POAG (glaucoma suspects) and/or dementia inhibit neurite outgrowth and promote a reactive astrocyte morphology by a mechanism which may involve activation of the RhoA/p160 ROCK signaling pathway.
- Subjects
AUTOANTIBODIES; DIABETES; GLAUCOMA; DEMENTIA research; ENDOTHELIAL cells
- Publication
Frontiers in Endocrinology, 2013, Vol 4, p1
- ISSN
1664-2392
- Publication type
Article
- DOI
10.3389/fendo.2013.00058