Focal Light-emitting-diode (LED)-induced cone photoreceptor degeneration in mice can be prevented with Brimonidine or trophic factors.

Abstract

Purpose: To investigate the effects of LED-induced phototoxicity (LIP) on cone photoreceptors and its neuroprotection with topical brimonidine (BMD) or intraocular Brain-Derived Neurotrophic Factor (BDNF), Ciliary Neurotrophic Factor (CNTF) or basic Fibroblast Growth Factor (bFGF).

Methods: Adult female Swiss mice were dark adapted overnight, anesthetized and their left pupil dilated with 1% tropicamide. The left eye was exposed to blue light (400nm) from a 10V LED (200 lux) placed at 1mm from the cornea during 10sec. The lesion was monitored using Spectral Domain Optic Coherence Tomography (SD-OCT Spectralis®) and 7 days later the retinas were incubated with antibodies against S-opsin. Because in albino mice, 23% of cones are genuine-S and the proportion of dual cones increases to 76% at the expense of genuine-L cones (4%) (Ortín-Martínez et al., 2014 PLoS One 9:e102392), S-opsin may be used to identify and estimate the total number of S- and/or L-cone photoreceptors. The left eyes were treated topically with BMD (1%) administered before or right after LIP or with vehicle, or intravitreally with BDNF (2.5µg), CNTF (0.2µg), bFGF (0.5µg) or the corresponding vehicle solutions, right after LIP. Seven days later, retinal whole mounts were examined and the numbers of S-immunolabelled cones counted automatically within predetermined fixed-size circular areas (with a radius of 0.4 mm) centered on the lesion in the left retinas or the corresponding region of their fellow right retinas.

Results: SD-OCT showed focal damage in a circular region of the superotemporal left retina that showed progressive thinning, from 209.6±5µm (day 0) to 165.4±8µm (day 7). In the wholemounts, the center of the lesion was found to be located at 0.8 mm from the optic disk and contained 2,174±558 (n=4) S-opsin immunolabelled cones in the LED exposed retinas and 5,780±839 (n=4) in the corresponding region of the contralateral retina. All the treatments used: topical BMD pre LIP (n=11) and post LIP (n=7) or intravitreal BDNF (n=8), CNTF (n=8) and bFGF (n=7) increased significantly S- cone survival.

Conclusions: LIP is a reliable and quantifiable model to study cone degeneration in adult mice, and topical BMD or intraocular BDNF, CNTF or bFGF can prevent cone loss.