Topical brimonidine or intravitreal bdnf, cntf, or bfgf protect cones against phototoxicity

Abstract

Purpose: 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). Methods: 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-1þ monocytic cells, TUNELþ cells and S-opsinþ 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 lg), CNTF (0.2 lg), bFGF (0.5 lg), or corresponding vehicle right after LIP. At 7 days, S-opsinþ cone outer segments were counted within predetermined fixed-size areas (PFA) centered on the lesion in both flattened retinas. Results: SD-OCT showed a circular region in the superior-temporal left retina with progressive thinning (207.9 6 5.6 lm to 160.7 6 6.8 lm [7 days], n ¼ 8), increasing TUNELþ cells (peak at 3 days), decreasing S-opsinþ cone outer segments, and strong microglia activation. ERGs were normal by 3 days. Total S-opsinþ cones in the PFA for LIP-treated and fellow-retinas were 2330 6 262 and 5601 6 583 (n ¼ 8), respectively. All neuroprotectants (n ¼ 7–11), including topical BMD pre-or post-LIP, or intravitreal BDNF, CNTF, and bFGF, showed significantly greater S-opsinþ cone survival than their corresponding vehicle-treated groups. Conclusions: LIP is a reliable, quantifiable focal photoreceptor degeneration model. Topical BMD or intravitreal BDNF, CNTF, or bFGF protect against LIP-induced cone-photoreceptor loss. Translational Relevance: Topical BMD or intravitreal BDNF, CNTF, or bFGF protect cones against phototoxicity.