title: Subclinical experimental optic neuropathy after accelerated proton beam irradiation.
abstract: BACKGROUND
  Accelerated proton beam irradiation has been used for several years to treat intraocular tumors. The pathophysiology of proton-beam-induced retinopathy and neuropathy has not been characterized to date. The present study investigates the early effects of irradiation with an accelerated proton beam on the optic nerve of the rabbit.
  
  
  METHODS
  The optic nerve head of Albino New Zealand rabbits (n = 14) was irradiated with a narrow beam of accelerated protons using the total dose of 60 and 43 Gy, respectively. This dose was split up into 4 equal sessions taking place on 4 consecutive days. Ophthalmoscopic examination was performed regularly, and the rabbits were sacrificed at 1, 3 and 8 months after irradiation. The eyes were enucleated and processed for light and electron microscopy.
  
  
  RESULTS
  Despite the absence of ophthalmoscopically detectable optic neuropathy in all 14 rabbits irrespective of the dose of irradiation, light and electron microscopy of the optic nerve showed a glial and fibrotic perivascular scar made up predominantly of altered astrocytes. This scar formation was seen as early as 1 month after irradiation and was at times accompanied by infiltration with inflammatory cells perivascularly both outside and within the optic nerve. In contrast to the astrocytes, oligodendrocytes did not show degenerative cellular alterations. During the 8-month follow-up, no signs of vascular occlusion were found.
  
  
  CONCLUSIONS
  The observed lesions in the glial tissues with consecutive fibrosis appear to stem from a direct effect of irradiation. This may represent the initial mechanism of early subclinical irradiation-induced damage to the optic nerve before vascular occlusions may occur at a later stage, which may lead to more severe damage.
authors.affiliation: Hôpital Ophtalmique Jules-Gonin, University of Lausanne, Switzerland.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wolfensberger
authors.forename: Martin
authors.initials: M
authors.lastname: Zwingli
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Egger
authors.forename: Pierre
authors.initials: P
authors.lastname: Schnyder
authors.forename: Leonidas
authors.initials: L
authors.lastname: Zografos
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000528:radiation effects / Q000648:ultrastructure; D001369:Axons / Q000473:pathology / Q000528:radiation effects / Q000648:ultrastructure; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000473:pathology / Q000648:ultrastructure; D009901:Optic Nerve Diseases / Q000473:pathology*; D011522:Protons; D011817:Rabbits; D011833:Radiation Injuries, Experimental / Q000473:pathology*; D013997:Time Factors
chemical_list: D011522:Protons