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Arturo Ortin-Martinez, F Javier Valiente-Soriano, Diego García-Ayuso, Manuel Jimenez-Lopez, Luis Alarcon-Martinez, Jose Manuel Bernal-Garro, Leticia Nieto-Lopez, Marta Agudo, Maria Paz Villegas-Perez, Manuel Vidal-Sanz; Cone neuroprotection afforded by Brimonidine and BDNF in a new model of focal Light-Emitting-Diode (LED)-induced phototoxicity. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4369.
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To investigate and compare neuroprotective effects of topical brimonidine (BMD) or intraocular Brain-derived-neurotrophic factor (BDNF) administration on the S- and L-cone population after LED- induced phototoxicity (LEDIP).
Adult female Sprague-Dawley rats were dark adapted overnight, anesthetized and their left pupil dilated with topical tropicamide (1%). The left retina was exposed to a 10V blue LED (200lux) placed at 1mm from the cornea during 10 seconds. Rats were treated three times a day (t.i.d.) with two 5µl drops of Brimonidine 1%, starting one day prior to (BMD pre-LEDIP group) or right after LEDIP (BMD post-LEDIP group). A third group received a single intravitreal injection (5µg) of Brain-Derived Neurotrophic Factor (BDNF) inmediatly after LEDIP (BDNF group). Additional groups were treated with topical (pre-LEDIP, post-LEDIP) or intravitreal Vehicle. For all groups n=7. One week after LEDIP retinas were prepared as whole mounts, and the S- and L-cones were immunodetected with antibodies against S- and L-opsin. The numbers of S- and L-cones were automatically counted in a circular area (with a radius of 1.3 or 1 mm for S-cones or L-cones, respectively) centered on the lesion in the left retinas and in a corresponding region in the right control retinas.
LEDIP produced a small circular region of cone degeneration in the superotemporal quadrant of the left retinas at 2.4 mm from the optic disc. The total numbers of S- or L-cones counted in the circular area centered in the lesion were 812±299 and 7,463±1,256 for the Vehicle pre-LEDIP group; 689±238 and 7,775±1,038 for the Vehicle post-LEDIP group; 569±184 and 6,651±2,904 for the intravitreally injected Vehicle group; 1578±361 and 9,024±1,405 for the BMD pre-LEDIP group; 1,444±296 and 9,007±1,453 for the BMD post-LEDIP group, and 1,229±509 and 9,710±3,725 for the BDNF group, respectively. There was a significantly increased survival of the S- and L-cones in both the BMD-preLEDIP and BMD-postLEDIP groups and also in the BDNF-treated group.
LEDIP targeted to the retinal area with highest L-cone density results in a severe focal loss of S- and L-cones that can be rescued significantly with intravitreal BDNF or with topical BMD administered prior to or right after light exposure.
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