Transient ischemia of the retina results in massive degeneration of the retinotectal projection: long-term neuroprotection with brimonidine

• Published in: Experimental neurology 2003-12, Vol.184 (2), p.767-777
• Main Authors: Avilés-Trigueros, Marcelino, Mayor-Torroglosa, Sergio, Garcı́a-Avilés, Antonio, Lafuente, Marı́a P, Rodrı́guez, Marı́a E, Miralles de Imperial, Jaime, Villegas-Pérez, Marı́a P, Vidal-Sanz, Manuel
• Format: Article
• Language: English
• Subjects: Afferent Pathways - drug effects; Afferent Pathways - pathology; Alpha-2 selective agonists; Animals; Anterograde axonal transport; Anterograde degeneration; Axonal Transport - drug effects; Biological and medical sciences; Brain Stem - drug effects; Brain Stem - pathology; Brimonidine; Brimonidine Tartrate; Cholera Toxin; Cholera toxin B subunit; Eye - blood supply; Female; Functional Laterality; Image Processing, Computer-Assisted; Immunohistochemistry; Ischemia - physiopathology; Ischemia - prevention & control; Medical sciences; Mesencephalon - drug effects; Mesencephalon - pathology; Nerve Degeneration - pathology; Nerve Degeneration - prevention & control; Neurology; Neuroprotection; Neuroprotective Agents - therapeutic use; Orthograde tracers; Quinoxalines - therapeutic use; Rats; Rats, Sprague-Dawley; Retina - drug effects; Retina - physiopathology; Retinal ganglion cell axons; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - pathology; Retinal Ganglion Cells - physiology; Retinal ischemia; Retinotectal system; Staining and Labeling; Superior colliculus
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/S0014-4886(03)00298-X

In adult rats, we have induced retinal ischemia and investigated anterogradely labeled surviving retinal ganglion cell (RGC) afferents to the contralateral superior colliculus (SC). The animals received topically in their left eyes two 5-μl drops of saline or saline-containing 0.5% brimonidine (BMD), 1 h before 90 min of retinal ischemia induced by ligature of the left ophthalmic vessels. Two months after ischemia, the anterogradely transported neuronal tracer cholera toxin B subunit (CTB) was injected in the ischemic eyes and animals were processed 4 days later. As controls and for comparison, the retinotectal innervation of unlesioned age-matched control rats was also examined with CTB. In control and experimental animals, serial coronal sections of the mesencephalon and brainstem were immunoreacted for CTB and the area and thickness of the two most superficial layers of the SC containing densely CTB-labeled profiles were estimated with an image analysis system. Ninety minutes of ischemia resulted 2 months later in reduced density of CTB-labeled profiles in the contralateral SC of the vehicle-treated rats, representing less than one half the area occupied by CTB-labeled profiles in control rats. This resulted in shrinkage of these layers and in the presence of areas virtually devoid of CTB immunoreactivity, suggesting orthograde degeneration of retinal terminals and/or decrease of anterograde axonal transport. Topical pretreatment with BMD resulted 2 months later in CTB immunoreactivity that occupied the superficial layers of the contralateral SC in an area of approximately 86% of that observed in the unlesioned control group of animals, indicating that BMD protects against ischemia-induced degeneration of the retinotectal projection, and preserves anterograde axonal transport.