scholarly journals The Aging Stress Response and Its Implication for AMD Pathogenesis

2020 ◽  
Vol 21 (22) ◽  
pp. 8840
Author(s):  
Janusz Blasiak ◽  
Elzbieta Pawlowska ◽  
Anna Sobczuk ◽  
Joanna Szczepanska ◽  
Kai Kaarniranta
Keyword(s):  
Stress Response ◽  
Vision Loss ◽  
The Elderly ◽  
Cellular Level ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Evolutionarily Conserved ◽  
Nutrient Signaling ◽  
Amp Activated Protein Kinase

Aging induces several stress response pathways to counterbalance detrimental changes associated with this process. These pathways include nutrient signaling, proteostasis, mitochondrial quality control and DNA damage response. At the cellular level, these pathways are controlled by evolutionarily conserved signaling molecules, such as 5’AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), insulin/insulin-like growth factor 1 (IGF-1) and sirtuins, including SIRT1. Peroxisome proliferation-activated receptor coactivator 1 alpha (PGC-1α), encoded by the PPARGC1A gene, playing an important role in antioxidant defense and mitochondrial biogenesis, may interact with these molecules influencing lifespan and general fitness. Perturbation in the aging stress response may lead to aging-related disorders, including age-related macular degeneration (AMD), the main reason for vision loss in the elderly. This is supported by studies showing an important role of disturbances in mitochondrial metabolism, DDR and autophagy in AMD pathogenesis. In addition, disturbed expression of PGC-1α was shown to associate with AMD. Therefore, the aging stress response may be critical for AMD pathogenesis, and further studies are needed to precisely determine mechanisms underlying its role in AMD. These studies can include research on retinal cells produced from pluripotent stem cells obtained from AMD donors with the mutations, either native or engineered, in the critical genes for the aging stress response, including AMPK, IGF1, MTOR, SIRT1 and PPARGC1A.

scholarly journals Introduction to the multi-author review on macular degeneration

2020 ◽  
Vol 77 (5) ◽  
pp. 779-780 ◽  
Author(s):  
Anu Kauppinen
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
The Elderly ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Severe Vision Loss ◽  
Author Review ◽  
Dry Amd ◽  
Endothelial Growth Factor

AbstractProlonged life expectancies contribute to the increasing prevalence of age-related macular degeneration (AMD) that is already the leading cause of severe vision loss among the elderly in developed countries. In dry AMD, the disease culminates into vast retinal atrophy, whereas the wet form is characterized by retinal edema and sudden vision loss due to neovascularization originating from the choroid beneath the Bruch’s membrane. There is no treatment for dry AMD and despite intravitreal injections of anti-vascular endothelial growth factor (VEGF) that suppress the neovessel formation, also wet AMD needs new therapies to prevent the disease progression and to serve patients lacking of positive response to current medicines. Knowledge on disease mechanisms is a prerequisite for the drug development, which is hindered by the multifactorial nature of AMD. Numerous distinguished publications have revealed AMD mechanisms at the cellular and molecular level and in this multi-author review, we take a bit broader look at the topic with some novel aspects.

scholarly journals Intravitreal Ranibizumab Treatment and Treatment Regimens in Wet-Form (Neovascular) Age-Related Macular Degeneration

2017 ◽  
pp. 189-197
Keyword(s):  
Macular Degeneration ◽  
Progressive Disease ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Therapeutic Tool ◽  
Intravitreal Ranibizumab ◽  
Treatment Regimens ◽  
Age Related ◽  
Ranibizumab Treatment

Age-related macular degeneration (AMD) is a chronic and progressive disease of the central retina that causes vision loss in people over 50 years of age. With an understanding of the role of VEGF in AMD, intravitreal anti-VEGF agents are used as the most important therapeutic tool in the management of AMD. In this review we try to discuss intravitreal ranibizumab treatment and treatment regimens in wet (neovascular) age-related macular degeneration.

scholarly journals Modern view on the etiopathogenesis of age-related macular degeneration and the role of molecular genetic determinants in it

2021 ◽  
Vol 9 (3) ◽  
pp. 21-27
Author(s):  
N.V. Malachkova ◽  
Mohammad Mashhour Mohammad Masa’deh ◽  
Osama Mohammad Miteb Al-Jarrah ◽  
H.P. Liudkevych ◽  
D.S. Sukhan
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
High Specificity ◽  
Age Related Macular Degeneration ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Age Related

Age-related macular degeneration mainly affects the elderly and is one of the most common causes of rapidly progressive vision loss. Over more than 150 years of research, the scientific community has gone from understanding the macroscopic picture of the lesion, presumable identification of drusen as the main morphological manifestation of nosology, to detailed classifications and determine the role of genetic determinants in the etiopathogenesis of the disease — high specificity, the possibility of preventive analysis, and much unclear in the field of genetic diagnosis of eye diseases determine the accurate attention of specialized research groups to the early diagnosis using genetic analysis. The review article was aimed to systematize the information about possible links in the pathogenesis of age-related macular degeneration and identify potential polymorphisms that can initiate and modulate the activity of these links. During the study, we could find out five main mechanisms of damage to the vascular membrane of the eye itself, which are affected by single nucleotide polymorphisms. The hig­hest affinity was shown by genetic variants of separate sites of CFH (rs1061170), HTRA1 (rs11200638), TNF (rs1800629), VEGFA (rs2010963). Literature data obtained from foreign and national sources indexed by Scopus, Web of Science databases, in particular for the last 5 years, pay special attention to these areas as potential predictors or modifiers of pathological processes involved in the process of macular degeneration. Despite the large number of studies examining the predisposition, pathogenesis, diagnosis, and treatment of age-related macular degeneration to stop the spread of vision loss, only a few issues are understood thoroughly. Considering the successful cases of application of biological and gene therapy for the management of such patients, we see new horizons in the detailed study of molecular interactions that underlie the pathology. The review confirms the active role of polymorphisms in one of the most relevant pathological processes of the human eye.

scholarly journals Mechanism of Inflammation in Age-Related Macular Degeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Francesco Parmeggiani ◽  
Mario R. Romano ◽  
Ciro Costagliola ◽  
Francesco Semeraro ◽  
Carlo Incorvaia ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Microglial Activation ◽  
Vision Loss ◽  
Dietary Habits ◽  
The United States ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Oxidized Lipoproteins ◽  
Severe Vision Loss

Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

Ophthalmopathology of the old people. Population research. Preliminary results

2021 ◽  
pp. 9-12
Author(s):  
M.M. Bikbov ◽  
◽  
T.R. Gilmanshin ◽  
R.M. Zainullin ◽  
G.M. Kazakbaeva ◽  
...  
Keyword(s):  
Old Age ◽  
Vision Loss ◽  
The Elderly ◽  
Developed Countries ◽  
Diagnostic Methods ◽  
Age Related Macular Degeneration ◽  
Ophthalmological Examination ◽  
Old People ◽  
Age Related ◽  
Region Of Residence

Currently, the percentage of old people is growing from year to year in developed countries their share ranges from 10 to 15% of the entire population. In connection with such trends the issue of old age should be given special attention. Purpose. Identify the main risk factors and assess the incidence of ophthalmopathology among the elderly. Material and methods. In Ufa Eye Research Institute was examined 1526 people over 85 years old. Ophthalmological examination included standard and additional diagnostic methods: ultrasound biometry, keratotopography, computed perimetry, ophthalmoscopy using a fundus camera, optical coherence tomography. Results. The main cause of vision loss in the elderly was cataract – 41.7%, followed by AMD – 32.6%, then glaucoma – 10.1%, other eye diseases – 8.1%, optic disc pathology – 54.1% and diabetic angioretinopathy – 2.4%. The most significant association of the ophthalmopathology development is associated with such factors as age, gender, region of residence, axial length of the eye. Conclusions. Timely detection of ophthalmic pathology among old people will allow to preserve the patients visual functions, increase the social rehabilitation level and ensure their active and creative longevity. Key words: old age, cataracts, age-related macular degeneration, glaucoma.

Non-Nutritional Medical Treatments in Dry-Form (Non-Neovascular) Age-Related Macular Degeneration

2017 ◽  
pp. 145-148
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
The Elderly ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Medical Treatments ◽  
Age Related ◽  
Dry Amd ◽  
Disease Study ◽  
Developed World

Age-related macular degeneration (AMD) is the major cause of blindness for the elderly population in the developed world. Although vision loss is mainly due to the neovascular form, dry AMD remains a challenge for ophthalmologists because of the lack of effective therapies. The Age-Related Eye Disease Study (AREDS) demonstrated the protective effect of dietary supplementation of antioxidants to slow down the progression of dry AMD. On the other hand, there has been no proven drug treatment for dry AMD to date. This review is aimed to discuss recent non-nutritional treatments for dry AMD and geographic atrophy.

scholarly journals Altered photoreceptor metabolism in mouse causes late stage age-related macular degeneration-like pathologies

2020 ◽  
Vol 117 (23) ◽  
pp. 13094-13104 ◽  
Author(s):  
Shun-Yun Cheng ◽  
Joris Cipi ◽  
Shan Ma ◽  
Brian P. Hafler ◽  
Rahul N. Kanadia ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Mammalian Target Of Rapamycin ◽  
The Elderly ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Photoreceptor Outer Segment ◽  
Metabolic Adaptations ◽  
Age Related ◽  
Disease Stages

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. While the histopathology of the different disease stages is well characterized, the cause underlying the progression, from the early drusen stage to the advanced macular degeneration stage that leads to blindness, remains unknown. Here, we show that photoreceptors (PRs) of diseased individuals display increased expression of two key glycolytic genes, suggestive of a glucose shortage during disease. Mimicking aspects of this metabolic profile in PRs of wild-type mice by activation of the mammalian target of rapamycin complex 1 (mTORC1) caused early drusen-like pathologies, as well as advanced AMD-like pathologies. Mice with activated mTORC1 in PRs also displayed other early disease features, such as a delay in photoreceptor outer segment (POS) clearance and accumulation of lipofuscin in the retinal-pigmented epithelium (RPE) and of lipoproteins at the Bruch’s membrane (BrM), as well as changes in complement accumulation. Interestingly, formation of drusen-like deposits was dependent on activation of mTORC1 in cones. Both major types of advanced AMD pathologies, including geographic atrophy (GA) and neovascular pathologies, were also seen. Finally, activated mTORC1 in PRs resulted in a threefold reduction in di-docosahexaenoic acid (DHA)–containing phospholipid species. Feeding mice a DHA-enriched diet alleviated most pathologies. The data recapitulate many aspects of the human disease, suggesting that metabolic adaptations in photoreceptors could contribute to disease progression in AMD. Identifying the changes downstream of mTORC1 that lead to advanced pathologies in mouse might present new opportunities to study the role of PRs in AMD pathogenesis.

scholarly journals Eph Receptors and Ephrins in Retinal Diseases

2021 ◽  
Vol 22 (12) ◽  
pp. 6207
Author(s):  
Radoslaw Kaczmarek ◽  
Pawel Gajdzis ◽  
Malgorzata Gajdzis
Keyword(s):  
Diabetic Retinopathy ◽  
Retinopathy Of Prematurity ◽  
The Elderly ◽  
Common Point ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Eph Receptors ◽  
Age Related ◽  
The Common

Retinal diseases are the leading cause of irreversible blindness. They affect people of all ages, from newborns in retinopathy of prematurity, through age-independent diabetic retinopathy and complications of retinal detachment, to age-related macular degeneration (AMD), which occurs mainly in the elderly. Generally speaking, the causes of all problems are disturbances in blood supply, hypoxia, the formation of abnormal blood vessels, and fibrosis. Although the detailed mechanisms underlying them are varied, the common point is the involvement of Eph receptors and ephrins in their pathogenesis. In our study, we briefly discussed the pathophysiology of the most common retinal diseases (diabetic retinopathy, retinopathy of prematurity, proliferative vitreoretinopathy, and choroidal neovascularization) and collected available research results on the role of Eph and ephrins. We also discussed the safety aspect of the use of drugs acting on Eph and ephrin for ophthalmic indications.

scholarly journals Cellular senescence in the aging retina and developments of senotherapies for age-related macular degeneration

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Keng Siang Lee ◽  
Shuxiao Lin ◽  
David A. Copland ◽  
Andrew D. Dick ◽  
Jian Liu
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Cellular Senescence ◽  
Vision Loss ◽  
Inflammatory Responses ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Age Related

AbstractAge-related macular degeneration (AMD), a degenerative disease in the central macula area of the neuroretina and the supporting retinal pigment epithelium, is the most common cause of vision loss in the elderly. Although advances have been made, treatment to prevent the progressive degeneration is lacking. Besides the association of innate immune pathway genes with AMD susceptibility, environmental stress- and cellular senescence-induced alterations in pathways such as metabolic functions and inflammatory responses are also implicated in the pathophysiology of AMD. Cellular senescence is an adaptive cell process in response to noxious stimuli in both mitotic and postmitotic cells, activated by tumor suppressor proteins and prosecuted via an inflammatory secretome. In addition to physiological roles in embryogenesis and tissue regeneration, cellular senescence is augmented with age and contributes to a variety of age-related chronic conditions. Accumulation of senescent cells accompanied by an impairment in the immune-mediated elimination mechanisms results in increased frequency of senescent cells, termed “chronic” senescence. Age-associated senescent cells exhibit abnormal metabolism, increased generation of reactive oxygen species, and a heightened senescence-associated secretory phenotype that nurture a proinflammatory milieu detrimental to neighboring cells. Senescent changes in various retinal and choroidal tissue cells including the retinal pigment epithelium, microglia, neurons, and endothelial cells, contemporaneous with systemic immune aging in both innate and adaptive cells, have emerged as important contributors to the onset and development of AMD. The repertoire of senotherapeutic strategies such as senolytics, senomorphics, cell cycle regulation, and restoring cell homeostasis targeted both at tissue and systemic levels is expanding with the potential to treat a spectrum of age-related diseases, including AMD.

scholarly journals The prevalence of eye diseases in the elderly population is a global problem of modernity

2021 ◽  
Vol 65 (1) ◽  
pp. 62-68
Author(s):  
Dmitry A. Konyaev ◽  
Evgenia B. Popova ◽  
Anton A. Titov ◽  
Nikolay M. Agarkov ◽  
Maksim M. Yablokov ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Practical Importance ◽  
Age Groups ◽  
The Elderly ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Scientific Review ◽  
Age Related ◽  
High Prevalence

The priority problem of various industrial and developing countries, which largely determine the health of the population and, above all, older age groups, is currently eye diseases. Most modern researchers consider age-related macular degeneration, glaucoma, and cataracts to be eye diseases. Socially significant eye diseases have a high prevalence and are the leading cause of blindness in various countries. Authors analyzed the prevalence of glaucoma, age-related macular degeneration, and cataracts according to domestic and foreign publications in recent years. The results of the studies considered in the scientific review indicate a continuing gain in socially significant eye diseases, the frequency of which increases with age. The high incidence of the studied pathology is observed in China, India, and Russia. The study shows socially significant eye diseases to be the most critical problem in various countries, including the Russian Federation. The relevance of this pathology will increase due to the ongoing aging of the population and an increase in their share in the demographic structure of many states. The high prevalence of age-related macular degeneration, cataracts, and glaucoma leads to an increase in the number of people on the planet with complete or partial vision loss, which significantly disrupts their social functioning and requires significant financial costs for treatment and ensuring an acceptable level and quality of life. The data presented in the review and obtained results are of practical importance for the organization of monitoring of eye diseases and the development of an appropriate state and health strategy.

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