title: Autoreactive antibodies and loss of retinal ganglion cells in rats induced by immunization with ocular antigens.
abstract: OBJECTIVE
  In an experimental autoimmune animal model, retinal ganglion cell (RGC) loss was induced through immunization with glaucoma-related antigens. The target of this study was to investigate the pathomechanism behind this decline and the serum antibody reactivity against ocular and neuronal tissues after immunization with glaucoma- and non-glaucoma-associated antigens.
  
  
  METHODS
  Rats immunized with optic nerve antigen homogenate (ONA) or keratin (KER) were compared to control rats (CO). Intraocular pressure (IOP) was measured, and the fundi were examined regularly. Four weeks afterward, cells were counted in retinal flat mounts. Retina, optic nerve, and brain sections from healthy animals and optic nerve sections from immunized animals were incubated with serum collected at different time points. The occurrence of autoreactive antibodies was examined. Signs of antibody deposits, microglia activation, and demyelination were sought in optic nerves of immunized animals. Brain sections were examined for abnormalities.
  
  
  RESULTS
  No IOP or fundus changes were observed. Animals immunized with ONA showed a significant cell loss compared with the CO group. Elevated autoreactive antibodies against retina, optic nerve, and brain were observed. Animals immunized with KER, despite their immunologic response against KER, demonstrated neither RGC loss, nor increased development of autoreactive antibodies. Optic nerve from animals immunized with ONA demonstrated antibody accumulation, glia activation, and demyelination. No such observations were made in the KER or CO groups. Brain sections were without pathologic findings.
  
  
  CONCLUSIONS
  Systemic autoimmunity against ocular and neuronal epitopes, mediated by accordant autoreactive antibodies, is involved in the inflammatory processes that cause RGC degeneration in this experimental animal model.
authors: Experimental Ophthalmology, Department of Ophthalmology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors: Panagiotis
authors: P
authors: Laspas
authors: Oliver W
authors: OW
authors: Gramlich
authors: Harald D
authors: HD
authors: Müller
authors: Clemens S
authors: CS
authors: Cuny
authors: Philip F
authors: PF
authors: Gottschling
authors: Norbert
authors: N
authors: Pfeiffer
authors: H Burkhard
authors: HB
authors: Dick
authors: Stephanie C
authors: SC
authors: Joachim
authors: Franz H
authors: FH
authors: Grus
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001921:Brain / Q000276:immunology; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005901:Glaucoma / Q000276:immunology* / Q000473:pathology*; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007429:Intraocular Pressure / Q000276:immunology; D007633:Keratins / Q000276:immunology*; D008297:Male; D017628:Microglia / Q000276:immunology / Q000473:pathology; D009410:Nerve Degeneration / Q000276:immunology / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009900:Optic Nerve / Q000276:immunology / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D012165:Retinal Ganglion Cells / Q000276:immunology* / Q000473:pathology*
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D007633:Keratins