Summary: Age‐related macular degeneration (AMD) is characterized by the formation of drusen, extracellular deposits associated with atrophy of the retinal pigmented epithelium (RPE), disturbance of the transepithelial barrier and photoreceptor death. Amyloid‐β (Aβ) is present in drusen but its role during AMD remains unknown. This study investigated the in vitro and in vivo effects of the oligomeric form of Aβ(1‐42) – OAβ(1‐42) – on RPE and found that it reduced mitochondrial redox potential and increased the production of reactive oxygen species, but did not induce apoptosis in RPE cell cultures. It also disorganized the actin cytoskeleton and halved occludin expression, markedly decreasing attachment capacity and abolishing the selectivity of RPE cell transepithelial permeability. Antioxidant pretreatment partially reversed the effects of OAβ(1‐42) on mitochondrial redox potential and transepithelial permeability. Subretinally injected OAβ(1‐42) induced pigmentation loss and RPE hypertrophy but not RPE cell apoptosis in C57BL/6 J mice. Rapid OAβ(1‐42)‐induced disorganization of cytoskeletal actin filaments was accompanied by decreased RPE expression of the tight junction proteins occludin and zonula occludens‐1 and of the visual cycle proteins cellular retinaldehyde‐binding protein and RPE65. The number of photoreceptors decreased by half within a few days. Our study pinpoints the role of Aβ in RPE alterations and dysfunctions leading to retinal degeneration and suggests that targeting Aβ may help develop selective methods for treating diseases involving retinal degeneration, such as AMD.

Traumatic brain injury (TBI) is the principal cause of death and disability in children and young adults. Clinical and preclinical research efforts have been carried out to understand the acute, life-threatening pathophysiological events happening after TBI. In the past few years, however, it was recognized that TBI causes significant morbidity weeks, months, or years after the initial injury, thereby contributing substantially to the overall burden of TBI and the decrease of life expectancy in these patients. Long-lasting sequels of TBI include cognitive decline/dementia, sensory-motor dysfunction, and psychiatric disorders, and most important for patients is the need for socio-economic rehabilitation affecting their quality of life. Cerebrovascular alterations have been described during the first week after TBI for direct consequence development of neuroinflammatory process in relation to brain edema. Within the brain–immune interactions, the complement system, which is a family of blood and cell surface proteins, participates in the pathophysiology process. In fact, the complement system is part of the primary defense and clearance component of innate and adaptive immune response. In this review, the complement activation after TBI will be described in relation to the activation of the microglia and astrocytes as well as the blood–brain barrier dysfunction during the first week after the injury. Considering the neuroinflammatory activity as a causal element of neurological handicaps, some major parallel lines of complement activity in multiple sclerosis and Alzheimer pathologies with regard to cognitive impairment will be discussed for chronic TBI. A better understanding of the role of complement activation could facilitate the development of new therapeutic approaches for TBI.

Age Related Macular Degeneration (AMD) is the first cause of social blindness in people aged over 65 leading to atrophy of retinal pigment epithelial cells (RPE), photoreceptors and choroids, eventually associated with choroidal neovascularization. Accumulation of undigested cellular debris within RPE cells or under the RPE (Drusen), oxidative stress and inflammatory mediators contribute to the RPE cell death. The major risk to develop AMD is the Y402H polymorphism of complement factor H (CFH). CFH interacting with oxidized phospholipids on the RPE membrane modulates the functions of these cells, but the exact role of CFH in RPE cell death and survival remain poorly understood. The aim of this study was to analyze the potential protective mechanism of CFH on RPE cells submitted to oxidative stress. Upon exposure to oxidized lipids 4-HNE (4-hydroxy-2-nonenal) derived from photoreceptors, both the human RPE cell line ARPE-19 and RPE cells derived from human induced pluripotent stem cells were protected from death only in the presence of the full length human recombinant CFH in the culture medium. This protective effect was independent from the membrane attack complex (MAC) formation. CFH maintained RPE cells tight junctions’ structure and regulated the caspase dependent apoptosis process. These results demonstrated the CFH anti-oxidative stress functions independently of its capacity to inhibit MAC formation.

As a part of the Central Nervous System, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer’s disease patients. More recently, it turned out that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer’s patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration and glaucoma, but also in the retinas of Alzheimer’s patients. In this review, we first briefly discuss the biogenesis of amyloid-beta, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation and vascular abnormalities) related to the neurotoxic effects of amyloid-beta. We finally highlight the common features shared by Alzheimer’s disease, age-related macular degeneration and glaucoma in the context of amyloid-beta amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a “window” to the brain.