Purpose: To develop a focal photoreceptor degeneration model by blue lightemitting 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-1 þ monocytic cells, TUNEL þ cells and S-opsin þ 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-opsin þ 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 TUNEL þ cells (peak at 3 days), decreasing S-opsin þ cone outer segments, and strong microglia activation. ERGs were normal by 3 days. Total S-opsin þ 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-opsin þ 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 conephotoreceptor loss. Translational Relevance: Topical BMD or intravitreal BDNF, CNTF, or bFGF protect cones against phototoxicity. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Signaling mediated by cytokines and chemokines is involved in glaucoma-associated neuroinflammation and in the damage of retinal ganglion cells (RGCs). Using multiplexed immunoassay and immunohistochemical techniques in a glaucoma mouse model at different time points after ocular hypertension (OHT), we analyzed (i) the expression of pro-inflammatory cytokines, anti-inflammatory cytokines, BDNF, VEGF, and fractalkine; and (ii) the number of Brn3a+ RGCs. In OHT eyes, there was an upregulation of (i) IFN-γ at days 3, 5, and 15; (ii) IL-4 at days 1, 3, 5, and 7 and IL-10 at days 3 and 5 (coinciding with downregulation of IL1-β at days 1, 5, and 7); (iii) IL-6 at days 1, 3, and 5; (iv) fractalkine and VEGF at day 1; and (v) BDNF at days 1, 3, 7, and 15. In contralateral eyes, there were (i) an upregulation of IL-1β at days 1 and 3 and a downregulation at day 7, coinciding with the downregulation of IL4 at days 3 and 5 and the upregulation at day 7; (ii) an upregulation of IL-6 at days 1, 5, and 7 and a downregulation at 15 days; (iii) an upregulation of IL-10 at days 3 and 7; and (iv) an upregulation of IL-17 at day 15. In OHT eyes, there was a reduction in the Brn3a+ RGCs number at days 3, 5, 7, and 15. OHT changes cytokine levels in both OHT and contralateral eyes at different time points after OHT induction, confirming the immune system involvement in glaucomatous neurodegeneration.

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