Age-related macular degeneration

Fleckenstein, Monika; Keenan, Tiarnán D L; Guymer, Robyn H.; Chakravarthy, Usha; Schmitz-Valckenberg, Steffen; Klaver, Caroline C W; Wong, Wai T; Chew, Emily Y.

doi:10.1038/s41572-021-00265-2

Cited by 473 publications

(456 citation statements)

References 258 publications

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“…The presence of photoreceptors that are rich in fatty acids makes the retina susceptible to oxidation [19]. In the same way, different pathologies that affect this tissue are closely related to inflammatory processes [20][21][22]. Therefore, many pathologies related to the posterior pole of the eye have been associated with these two processes, sharing their pathophysiology not only in oxidative stress but also in inflammation phenomena.…”

Section: Oxidative Stress and Inflammationmentioning

confidence: 99%

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

et al. 2021

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Most irreversible blindness observed with glaucoma and retina-related ocular diseases, including age-related macular degeneration and diabetic retinopathy, have their origin in the posterior segment of the eye, making their physiopathology both complex and interconnected. In addition to the age factor, these diseases share the same mechanism disorder based essentially on oxidative stress. In this context, the imbalance between the production of reactive oxygen species (ROS) mainly by mitochondria and their elimination by protective mechanisms leads to chronic inflammation. Oxidative stress and inflammation share a close pathophysiological process, appearing simultaneously and suggesting a relationship between both mechanisms. The biochemical end point of these two biological alarming systems is the release of different biomarkers that can be used in the diagnosis. Furthermore, oxidative stress, initiating in the vulnerable tissue of the posterior segment, is closely related to mitochondrial dysfunction, apoptosis, autophagy dysfunction, and inflammation, which are involved in each disease progression. In this review, we have analyzed (1) the oxidative stress and inflammatory processes in the back of the eye, (2) the importance of biomarkers, detected in systemic or ocular fluids, for the diagnosis of eye diseases based on recent studies, and (3) the treatment of posterior ocular diseases, based on long-term clinical studies.

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Section: Oxidative Stress and Inflammationmentioning

confidence: 99%

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

et al. 2021

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“…As mentioned, anti-VEGF therapy is applied in wet AMD cases. Dry AMD, which accounts for about 85% of all AMD cases at diagnosis, has very limited therapeutic options, and these include antioxidant, vitamin, and mineral diet supplementation (reviewed in [27][28][29]). However, the results of these treatments are still ambiguous and studies on new molecular therapeutic targets are warranted.…”

Section: Age-related Macular Degenerationmentioning

confidence: 99%

Potential of Telomerase in Age-Related Macular Degeneration—Involvement of Senescence, DNA Damage Response and Autophagy and a Key Role of PGC-1α

Błasiak

Szczepańska

Fila

et al. 2021

IJMS

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Age-related macular degeneration (AMD), the main cause of vision loss in the elderly, is associated with oxidation in the retina cells promoting telomere attrition. Activation of telomerase was reported to improve macular functions in AMD patients. The catalytic subunit of human telomerase (hTERT) may directly interact with proteins important for senescence, DNA damage response, and autophagy, which are impaired in AMD. hTERT interaction with mTORC1 (mTOR (mechanistic target of rapamycin) complex 1) and PINK1 (PTEN-induced kinase 1) activates macroautophagy and mitophagy, respectively, and removes cellular debris accumulated over AMD progression. Ectopic expression of telomerase in retinal pigment epithelium (RPE) cells lengthened telomeres, reduced senescence, and extended their lifespan. These effects provide evidence for the potential of telomerase in AMD therapy. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may be involved in AMD pathogenesis through decreasing oxidative stress and senescence, regulation of vascular endothelial growth factor (VEGF), and improving autophagy. PGC-1α and TERT form an inhibitory positive feedback loop. In conclusion, telomerase activation and its ectopic expression in RPE cells, as well as controlled clinical trials on the effects of telomerase activation in AMD patients, are justified and should be assisted by PGC-1α modulators to increase the therapeutic potential of telomerase in AMD.

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“…Currently, at least half a million people suffer from advanced AMD, with numbers expected to climb in increasingly aged populations. Although the exact pathogenesis and aetiology of AMD are not well understood, the disease clearly affects choriocapillaris, Bruch's membrane (the lamina between choroid and RPE), RPE and photoreceptors, and ultimately destroys the macula leading to loss of the high acuity vision (Fleckenstein et al, 2021). RPE dysfunction is at the heart of AMD pathogenesis, leading to photoreceptor death (from its apical side) and to atrophy of the choroid capillaries (from its basolateral side).…”

Section: Age-related Macular Degenerationmentioning

confidence: 99%

“…Ca. 35% of AMD patients have at-risk polymorphisms in the gene of complement factor H, suggesting that decreased innate immunity is linked with the disease (Fleckenstein et al, 2021). Another polymorphism associated with AMD is found in the ARMS2 gene, pointing to potential dysfunctional mitochondrial energy metabolism (Micklisch et al, 2017).…”

Section: Age-related Macular Degenerationmentioning

confidence: 99%

Galectins in the Pathogenesis of Common Retinal Disease

et al. 2021

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Diseases of the retina are major causes of visual impairment and blindness in developed countries and, due to an ageing population, their prevalence is continually rising. The lack of effective therapies and the limitations of those currently in use highlight the importance of continued research into the pathogenesis of these diseases. Vascular endothelial growth factor (VEGF) plays a major role in driving vascular dysfunction in retinal disease and has therefore become a key therapeutic target. Recent evidence also points to a potentially similarly important role of galectins, a family of β-galactoside-binding proteins. Indeed, they have been implicated in regulating fundamental processes, including vascular hyperpermeability, angiogenesis, neuroinflammation, and oxidative stress, all of which also play a prominent role in retinopathies. Here, we review direct evidence for pathological roles of galectins in retinal disease. In addition, we extrapolate potential roles of galectins in the retina from evidence in cancer, immune and neuro-biology. We conclude that there is value in increasing understanding of galectin function in retinal biology, in particular in the context of the retinal vasculature and microglia. With greater insight, recent clinical developments of galectin-targeting drugs could potentially also be of benefit to the clinical management of many blinding diseases.

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Age-related macular degeneration

Cited by 473 publications

References 258 publications

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

Potential of Telomerase in Age-Related Macular Degeneration—Involvement of Senescence, DNA Damage Response and Autophagy and a Key Role of PGC-1α

Galectins in the Pathogenesis of Common Retinal Disease

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