Effect of experimental glaucoma on the visual pathway function and superior colliculus glial structure

BORDONE, MELINA; GONZÁLEZ FLEITAS MF; ROSENSTEIN, RUTH

Seattle

Congreso; 2013 ARVO Annual Meeting; 2013

Association for Research in Vision and Ophthalmology (ARVO)

Classically,glaucoma has been conceived as a disease limited to the eye. However, axons of retinal ganglion cells (RGCs)have extraorbital and intracranial components. In the rat,over 90% of RGCs axons project to the contralateral superior colliculus (SC). We have developed an experimental rat model of glaucoma through weekly intracameral injections of Chondroitin sulfate (CS), which mimics central aspects of human glaucoma. The purpose of this work was to study the effects of ocular hypertension on visual pathway function and SC structure.Methods Male Wistar rats were injected with vehicle or CS in the anterior chamber once a week for 15 weeks. Intraocular pressure (IOP) was assessed with a TonoPen, and flash visual evoked potentials (VEPs) were registered with skull-implanted electrodes. In addition, retinal anterograde transport was examined after an intravitreal injection of β-subunit cholera toxin. An immunohistochemical analysis of Iba1 (microglia activation marker) and glial fibrillary acidic protein (GFAP) levels in the SC were performed. An histochemical analysis of Griffonia simplicifolia agglutinin (GSA)-lectin levels was also in the SC were performed. Results: Ocular hypertension induced a significant decrease in VEP N2-P2 component amplitude at 6 weeks and a further decrease was observed at 15 weeks. Anterograde transport to the SC significantly decreased after 6 weeks of treatment, and was completely abolished at 15 weeks of ocular hypertension. Iba1- immunoreactivity significantly increased in the SC that receives axons from the glaucomatous eye at 6 and 15 weeks of ocular hypertension, which correlated with a significant increase in iba1-positive cell number but not with iba1 expression level/cell. A similar pattern was observed with GSA-lectin levels. A pronounced astroglial response (GFAP levels) was evident in the SC at 15 (but not 6) weeks of hypertension. Conclusions: These results suggest a "misconnection" between the retina and the superior visual pathway at early stages of ocular hypertension (when the number of RGCs remains unchanged), accompanied by an early microglial response and more delayed astroglial alterations in the SC.