Abstract
Abstract: :
Purpose: To develop a mouse model of glaucoma. Methods: We induced obstruction of aqueous humor outflow in adult C57Bl6/J mice by combining injection of indocyanine green dye (ICG) into the anterior chamber, followed by diode laser treatment of the trabecular meshwork and episcleral veins enriched with the dye. Mice received either 60 or 100 laser applications. To evaluate aqueous humor flow, fluorophotometry was performed with a slit-lamp biomicroscope equipped with a high integration CCD camera. Fluorescence was measured at 15min intervals after topical application of the fluorescein by iontophoresis in control and laser-cauterization treated animals. The function of the retina and optic nerve was evaluated with electroretinography and computerized pupillometry. Results: Fluorescein clearance was decreased in mice after laser-induced surgery (n=6). A consensual pupillary response was present in normal mice (n=11), the indirect response being 4.7±0.7% smaller than the direct; this allowed us to record the pupil of the unoperated eye in response to a light stimulus to each eye. Animals receiving laser-treatment without ICG (n=5) or ICG without laser (n=5) did not develop relative afferent pupillary defects or ERG amplitude deficits. Operated animals receiving 60 laser pulses (n=8) with ICG had developed a relative afferent pupillary defect (consensual = 8 ± 0.35% of direct) 7 days after surgery, which increased to 8.7±0.89% by 60 days and to 12.5±1.38% by 90 days after surgery. ERG amplitudes were decreased in operated eyes (control eyes a-wave:120±10µV, b-wave:348±27µV; operated eyes: 7d:a-36±6µV, b-121±25µV, 60d:a-28±7µV, b-168±25µV; 90d:54±18µV, b-172±56µV). Animals receiving 100 laser pulses with ICG developed a more severe deficit. Fifteen days after surgery, the operated eyes had developed relative afferent pupillary defects (consensual =9.8±2.1% smaller than direct) and ERG amplitude deficits (control eyes: a-210±20 µV, b-530±50 µV; operated eyes: a-30±10µV, b-90±50µV). Operated eyes had an almost complete relative afferent pupillary defect by 30 days postoperatively, with unchanged ERG amplitudes (operated eyes: a-50±26µV, b-105±50µV). Conclusion: Diode laser treatment of ICG saturated trabecular meshwork and episcleral veins causes a measurable visual deficit in the mouse, and may lead to an experimental model of retinal and optic nerve damages that mimic glaucoma.
Keywords: 316 animal model • 487 neuro-ophthalmology: optic nerve • 535 pupillary reflex