scholarly journals Melatonin in Retinal Physiology and Pathology: The Case of Age-Related Macular Degeneration

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Janusz Blasiak ◽  
Russel J. Reiter ◽  
Kai Kaarniranta
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Protective Role ◽  
Premature Aging ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Established Role

Melatonin, an indoleamine, is synthesized mainly in the pineal gland in a circadian fashion, but it is produced in many other organs, including the retina, which seems to be especially important as the eye is a primary recipient of circadian signals. Melatonin displays strong antioxidative properties, which predispose it to play a protective role in many human pathologies associated with oxidative stress, including premature aging and degenerative disease. Therefore, melatonin may play a role in age-related macular degeneration (AMD), a disease affecting photoreceptors, and retinal pigment epithelium (RPE) with an established role of oxidative stress in its pathogenesis. Several studies have shown that melatonin could exert the protective effect against damage to RPE cells evoked by reactive oxygen species (ROS), but it has also been reported to increase ROS-induced damage to photoreceptors and RPE. Melatonin behaves like synthetic mitochondria-targeted antioxidants, which concentrate in mitochondria at relatively high levels; thus, melatonin may prevent mitochondrial damage in AMD. The retina contains telomerase, an enzyme implicated in maintaining the length of telomeres, and oxidative stress inhibits telomere synthesis, while melatonin overcomes this effect. These features support considering melatonin as a preventive and therapeutic agent in the treatment of AMD.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

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.

scholarly journals Photo-damage, photo-protection and age-related macular degeneration

2015 ◽  
Vol 14 (9) ◽  
pp. 1560-1577 ◽  
Author(s):  
Melisa D. Marquioni-Ramella ◽  
Angela M. Suburo
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Molecular Targets ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Photo Damage ◽  
Effect Of Light

The course of Age-related Macular Degeneration (AMD) is described as the effect of light (400–580 nm) on various molecular targets in photoreceptors and the retinal pigment epithelium (RPE). Photo-damage is followed by inflammation, increasing oxidative stress and, probably, unveiling new photosensitive molecules.

scholarly journals Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Janusz Blasiak ◽  
Goran Petrovski ◽  
Zoltán Veréb ◽  
Andrea Facskó ◽  
Kai Kaarniranta
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Developed Countries ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
The Rich

Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE), Bruch’s membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD.

scholarly journals Subthreshold Nano-Second Laser Treatment and Age-Related Macular Degeneration

2021 ◽  
Vol 10 (3) ◽  
pp. 484
Author(s):  
Amy C. Cohn ◽  
Zhichao Wu ◽  
Andrew I. Jobling ◽  
Erica L. Fletcher ◽  
Robyn H. Guymer
Keyword(s):  
Macular Degeneration ◽  
Laser Treatment ◽  
Short Pulse ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Nanosecond Laser ◽  
Age Related ◽  
Short Pulse Lasers

The presence of drusen is an important hallmark of age-related macular degeneration (AMD). Laser-induced regression of drusen, first observed over four decades ago, has led to much interest in the potential role of lasers in slowing the progression of the disease. In this article, we summarise the key insights from pre-clinical studies into the possible mechanisms of action of various laser interventions that result in beneficial changes in the retinal pigment epithelium/Bruch’s membrane/choriocapillaris interface. Key learnings from clinical trials of laser treatment in AMD are also summarised, concentrating on the evolution of laser technology towards short pulse, non-thermal delivery such as the nanosecond laser. The evolution in our understanding of AMD, through advances in multimodal imaging and functional testing, as well as ongoing investigation of key pathological mechanisms, have all helped to set the scene for further well-conducted randomised trials to further explore potential utility of the nanosecond and other subthreshold short pulse lasers in AMD.

scholarly journals Mechanism of Inflammation in Age-Related Macular Degeneration: An Up-to-Date on Genetic Landmarks

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Francesco Parmeggiani ◽  
Francesco S. Sorrentino ◽  
Mario R. Romano ◽  
Ciro Costagliola ◽  
Francesco Semeraro ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Complex Disease ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Basic Research ◽  
Cholesterol Homeostasis ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Immune Mediated

Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment among people over 50 years of age, accounting for up to 50% of all cases of legal blindness in Western countries. Although the aging represents the main determinant of AMD, it must be considered a multifaceted disease caused by interactions among environmental risk factors and genetic backgrounds. Mounting evidence and/or arguments document the crucial role of inflammation and immune-mediated processes in the pathogenesis of AMD. Proinflammatory effects secondary to chronic inflammation (e.g., alternative complement activation) and heterogeneous types of oxidative stress (e.g., impaired cholesterol homeostasis) can result in degenerative damages at the level of crucial macular structures, that is photoreceptors, retinal pigment epithelium, and Bruch’s membrane. In the most recent years, the association of AMD with genes, directly or indirectly, involved in immunoinflammatory pathways is increasingly becoming an essential core for AMD knowledge. Starting from the key basic-research notions detectable at the root of AMD pathogenesis, the present up-to-date paper reviews the best-known and/or the most attractive genetic findings linked to the mechanisms of inflammation of this complex disease.

scholarly journals Mitophagy in the Retinal Pigment Epithelium of Dry Age-Related Macular Degeneration Investigated in the NFE2L2/PGC-1α-/- Mouse Model

2020 ◽  
Vol 21 (6) ◽  
pp. 1976 ◽  
Author(s):  
Iswariyaraja Sridevi Gurubaran ◽  
Johanna Viiri ◽  
Ali Koskela ◽  
Juha M.T. Hyttinen ◽  
Jussi J. Paterno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Double Knockout ◽  
Rpe Cells ◽  
Age Related

Increased oxidative stress and mitochondrial damage are observed in protein aggregation diseases, such as age-related macular degeneration (AMD). We have recently reported elevated levels of oxidative stress markers, damaged mitochondria, accumulating lysosomal lipofuscin and extracellular drusen-like structures in the retinal pigment epithelial cells (RPE) of the dry AMD-resembling NFE2L2/PGC1α double knockout (dKO) mouse model. Here, we provide evidence of a disturbance in the autolysosomal machinery handling mitochondrial clearance in the RPE cells of one-year-old NFE2L2/PGC1α-deficient mice. Confocal immunohistochemical analysis revealed an upregulation of autophagosome marker microtubule-associated proteins 1A/1B light chain 3B (LC3B) as well as numerous mitophagy markers, such as PTE-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase (PARKIN) together with damaged mitochondria. However, we detected no evidence of increased autolysosome formation in transmission electron micrographs or of colocalization of lysosomal marker LAMP2 (lysosome-associated membrane protein 2) and the mitochondrial marker ATP synthase β in confocal micrographs. Interestingly, we observed an upregulation of late autolysosomal fusion Ras-related protein (Rab7) in the perinuclear space of RPE cells together with autofluorescence aggregates. Our results reveal that there is at least a relative decrease of mitophagy in the RPE cells of NFE2L2/PGC1α dKO mice. This further supports the hypothesis that mitophagy is a putative therapy target in AMD-like pathology.

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