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H. Yamamoto, R. Schmidt–Kastner, D. Hamasaki, H. Yamamoto, J.–M. Parel; Complex Neurodegeneration in Retina Following Chronic Moderate Ischemia Induced by Bilateral Common Carotid Artery Occlusion in Rats . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1644.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: :Moderate retinal ischemia occurs in chronic carotid artery disease and intraretinal vascular conditions. To study the effect of moderate ischemia, bilateral common carotid artery occlusion (BCCAO) was performed, and the retina was analyzed at different times by histological and immunohistochemical methods. Methods: Under halothane anesthesia, the common carotid artery was tied off bilaterally in young male Wistar rats. Rats were perfused–fixed with paraformaldehyde at 3, 6 and 24 h (n=4), 1 week (w), and 2, 4, and 6 m (months; n=7 or more) after BCCAO along with matched sham controls. Paraffin sections stained with H&E were used to quantify the thickness and numbers of nuclei in the different retinal layers. Immunohistochemistry was performed with marker proteins for neurons (MAP2, parvalbumin–PV, ChAT, calbindin, synaptophysin), and astrocytes (GFAP). Antibodies to Hsp70, Hsp27, ubiquitin, Cox–2, and activated caspase–3, and a lectin method for microglia were used to study acute reactions. Cell counts and optical density measurements of immunolabeled sections were made and differences analyzed statistically. Results: Damage in the ganglion cell layer (GCL) developed after 1 w (40–50%; P < 0.01) and stabilized at this level. Changes in the inner nuclear layer (INL) were significant at 2 m (70–80%; P <0.02). Cell loss in the outer nuclear layer (ONL) emerged after 2 m of BCCAO (80–90%; P < 0.01) and was progressive (after 6 m, 60%; P < 0.0002). PV– and ChAT–labeled amacrine cells remained stable up to 2 m. Increased GFAP labeling of Mueller cells was seen after 1 w. Caspase–3 activation was noted in scattered ganglion cells at 1 d, and Cox–2 increased in the inner retina at 1 d. Activated microglial cells were seen by 6 h. Conclusions: BCCAO induced a progressive but incomplete neurodegeneration in the retina of Wistar rats. The time course and localization of cell damage in BCCAO differs from models of transient, severe retinal ischemia. It remains to be determined whether cell death is due to a slowly progressive metabolic deficit or due to repeated episodes of increased neural activity in face of reduced metabolic supplies. Support in part by: NIH– NS05820–36S1; Florida Lions Eye Bank, NIH center grant P30–EY014801; Corneal SA, Paris, France; Research to Prevent Blindness; Henri and Flore Lesieur Foundation.
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