title: Optic nerve infarction and post-ischemic inflammation in the rodent model of anterior ischemic optic neuropathy (rAION).
abstract: Nonarteritic anterior ischemic optic neuropathy (NAION) results from isolated anterior optic nerve (ON)-axonal ischemia near the retina-optic nerve junction. We utilized a rodent model of NAION (rAION) to study the in vivo inflammatory response after pure axonal ischemic infarct. ON ischemia was generated using laser-coupled rose Bengal dye photoactivation, and the infarct localized using tetrazolium red and histology. ON inflammation was evaluated following infarct using extrinsic macrophage (ED1) and microglial (isolated Iba1) cell markers. In naive ONs, some ED1(+)/Iba1(+) cells, representing extrinsic macrophages, were present in intraretinal ON region, but not in the retroscleral (isolated ON) region. Numerous ED1(-)/Iba1(+) cells, likely representing intrinsic microglia, were present throughout the entire ON. One day post-stroke, slight increases in both ED1(+) and Iba1(+) cells were apparent in the eye region immediately surrounding the anterior ON. Three days post-stroke, there was marked infiltration and aggregates of ED1(+)/Iba1(+) cells, with axon structural disruption in the region of the ischemic infarct. ED1(+) and Iba1(+) cells were present in the portion of the ON surrounding the infarct, possibly representing a penumbral region similar to that seen in ischemic brain infarcts. Although ED1(+) cells decreased by 7-14 days post-stroke, large numbers of Iba1(+) cells persisted in the anterior ON. Similar to other CNS ischemic strokes, pure axonal ischemia results in the early recruitment of extrinsic macrophages to the ischemic region. Manipulation of the inflammatory response may be an important variable that could potentially improve visual outcome.
authors.affiliation: Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, MD 21287, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Neil R
authors.initials: NR
authors.lastname: Miller
authors.forename: Steven L
authors.initials: SL
authors.lastname: Bernstein
mesh_terms: D000818:Animals; D001369:Axons / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D005455:Fluorescent Antibody Technique; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D017628:Microglia / Q000473:pathology; D009900:Optic Nerve / Q000098:blood supply / Q000276:immunology / Q000473:pathology*; D018917:Optic Neuropathy, Ischemic / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000276:immunology / Q000473:pathology*; D012395:Rose Bengal / Q000633:toxicity; D013997:Time Factors
chemical_list: D012395:Rose Bengal