Topical Brimonidine or Intravitreal BDNF, CNTF, or bFGF Protect Cones Against Phototoxicity

To develop a focal photoreceptor degeneration model by blue light-emitting diode (LED)-induced phototoxicity (LIP) and investigate the protective effects of topical brimonidine (BMD) or intravitreal brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), or basic fibroblast growth factor (bFGF). In anesthetized, dark-adapted, adult female Swiss mice, the left eye was dilated and exposed to blue light (10 seconds, 200 lux). After LIP, full-field electroretinograms (ERG) and spectral-domain optical coherence tomography (SD-OCT) were obtained longitudinally, and reactive-Iba-1 monocytic cells, TUNEL cells and S-opsin cone outer segments were examined up to 7 days. Left eyes were treated topically with BMD (1%) or vehicle, before or right after LIP, or intravitreally with BDNF (2.5 μg), CNTF (0.2 μg), bFGF (0.5 μg), or corresponding vehicle right after LIP. At 7 days, S-opsin cone outer segments were counted within predetermined fixed-size areas (PFA) centered on the lesion in both flattened retinas. SD-OCT showed a circular region in the superior-temporal left retina with progressive thinning (207.9 ± 5.6 μm to 160.7 ± 6.8 μm [7 days], = 8), increasing TUNEL cells (peak at 3 days), decreasing S-opsin cone outer segments, and strong microglia activation. ERGs were normal by 3 days. Total S-opsin cones in the PFA for LIP-treated and fellow-retinas were 2330 ± 262 and 5601 ± 583 ( = 8), respectively. All neuroprotectants ( = 7-11), including topical BMD pre- or post-LIP, or intravitreal BDNF, CNTF, and bFGF, showed significantly greater S-opsin cone survival than their corresponding vehicle-treated groups. LIP is a reliable, quantifiable focal photoreceptor degeneration model. Topical BMD or intravitreal BDNF, CNTF, or bFGF protect against LIP-induced cone-photoreceptor loss. Topical BMD or intravitreal BDNF, CNTF, or bFGF protect cones against phototoxicity.