Polydopamine Nanoparticles as Mimicking RPE Melanin for the Protection of Retinal Cells Against Blue Light-Induced Phototoxicity.

Exposure of the eyes to blue light can induce the overproduction of reactive oxygen species (ROS) in the retina and retinal pigment epithelium (RPE) cells, potentially leading to pathological damage of age-related macular degeneration (AMD). While the melanin in RPE cells absorbs blue light and prevents ROS accumulation, the loss and dysfunction of RPE melanin due to age-related changes may contribute to photooxidation toxicity. Herein, a novel approach utilizing a polydopamine-replenishing strategy via a single-dose intravitreal (IVT) injection is presented to protect retinal cells against blue light-induced phototoxicity. To investigate the effects of overexposure to blue light on retinal cells, a blue light exposure Nrf2-deficient mouse model is created, which is susceptible to light-induced retinal lesions. After blue light irradiation, retina degeneration and an overproduction of ROS are observed. The polydopamine-replenishing strategy demonstrated effectiveness in maintaining retinal structural integrity and preventing retina degeneration by reducing ROS production in retinal cells and limiting the phototoxicity of blue light exposure. These findings highlight the potential of polydopamine as a simple and effective replenishment for providing photoprotection against high-energy blue light exposure.

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

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-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. RESULTS: 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], n = 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 (n = 8), respectively. All neuroprotectants (n = 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. 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.