title: Anti-neurotrophic effects from autoantibodies in adult diabetes having primary open angle glaucoma or dementia.
abstract: OBJECTIVE
  To test for anti-endothelial and anti-neurotrophic effects from autoantibodies in subsets 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 outgrowth 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 10 μM concentrations of Y27632 (n = 4). It was substantially reduced by 30 mM 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 5 μM concentrations of Y27632.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical Service, New Jersey Health Care System, Department of Veterans Affairs Lyons, NJ, USA ; Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey New Brunswick, NJ, USA.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Zimering
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Moritz
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Donnelly
keywords: autoantibodies; dementia; diabetes mellitus; neurite outgrowth; open angle glaucoma