The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

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were up-regulated as consequence of light exposure. Their expression could depend on the degeneration processes ongoing after light exposure.

Retinal pigment epithelium (RPE) dysfunction and degeneration underlie the development of age-related macular degeneration (AMD), which is the leading cause of blindness worldwide. In this study, we investigated whether cerium oxide nanoparticles (CeO2-NPs or nanoceria), which are anti-oxidant agents with auto-regenerative properties, are able to preserve the RPE. On ARPE-19 cells, we found that CeO2-NPs promoted cell viability against H2O2–induced cellular damage. For the in vivo studies, we used a rat model of acute light damage (LD), which mimics many features of AMD. CeO2-NPs intravitreally injected three days before LD prevented RPE cell death and degeneration and nanoceria labelled with fluorescein were found localized in the cytoplasm of RPE cells. CeO2-NPs inhibited epithelial-mesenchymal transition of RPE cells and modulated autophagy by the down-regulation of LC3B-II and p62. Moreover, the treatment inhibited nuclear localization of LC3B. Taken together, our study demonstrates that CeO2-NPs represent an eligible candidate to counteract RPE degeneration and, therefore, a powerful therapy for AMD.

Cerium oxide nanoparticles (CeO 2-NPs; or nanoceria) have been largely studied for biomedical applications due to their peculiar auto-regenerative antioxidant activity. This review focuses on ophthalmic applications of nanoceria. Many in vivo data indicate that nanoceria protect the retina from neurodegeneration. In particular, they have been tested in animal models of age-related macular degeneration and retinitis pigmentosa and their neuroprotective properties have been shown to persist for a long time, without any collateral effects. In vitro cytotoxicity studies have shown that CeO 2-NPs could be safe for lens cells and could represent a new therapy for cataract treatment, but further studies are needed. To date, different pharmaceutical formulations based on nanoceria have been created looking at future clinical ophthalmic applications, such as water-soluble nanoceria, glycol chitosan-coated ceria nanoparticles (GCCNPs), and alginate-gelatin hydrogel loaded GCCNPs. GCCNPs were also effective in preventing choroidal neovascularization in vivo. Based on the nanosize of nanoceria, corneal permeation could be achieved to allow topical treatment of nanoceria. PEGylation and encapsulation in liposomes represent the main strategies to support corneal permeation, without altering nanoceria chemicalphysical properties. Based on their great antioxidant properties, safety, and nanosize, nanoceria represent a new potential therapeutic for the treatment of several eye disorders.

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We investigated whether treatment with brain-derived neurotrophic factor (BDNF), which is known to protect spiral ganglion cells (SGCs), could also protect hair cells (HCs) and supporting cells (SCs) in the organ of Corti of a guinea pig model of sensorineural hearing loss. Hearing loss was induced by administration of kanamycin/furosemide and two BDNF treatments were performed: (1) by gelatin sponge (BDNF-GS) with acute cochlear implantation (CI), and (2) through a mini-osmotic pump (BDNF-OP) with chronic CI. Outer HCs (OHCs), inner HCs (IHCs), Border, Phalangeal, Pillar, Deiters’, and Hensen’s cells were counted. The BDNF-GS cochleas had significantly fewer OHCs compared to the untreated ones, while the IHC and SC numbers did not differ between treated and untreated cochleas. The BDNF-OP group showed similar cell numbers to the untreated group. SGC packing density was not correlated with the total number of SCs for either BDNF group. Our data suggest that: (1) BDNF does not prevent cell death in the organ of Corti, and that the protection of SGCs could result from a direct targeting by BDNF; (2) BDNF might induce a different function/activity of the remaining cells in the organ of Corti (independently from cell number).