Interplay between aging and other factors of the pathogenesis of age-related macular degeneration

Błasiak, Janusz; Sobczuk, Piotr; Pawłowska, Elżbieta

doi:10.1016/j.arr.2022.101735

Cited by 38 publications

(11 citation statements)

References 220 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although age is considered the most important contributing risk factor for AMD, how age impacts the disease development of AMD and how to suppress this process are still not well understood. 43 , 44 In fact, the accumulation of senescent cells in human eyes with AMD is increasingly recognized. 45 Emerging studies indicate that senescence may directly and indirectly lead to the dysfunction and degeneration of various ocular tissues and cells, which greatly weaken their ability to maintain local homeostasis, resulting in progressive macular damage.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Benefit of Melatonin in Choroidal Neovascularization During Aging Through the Regulation of Senescent Macrophage/Microglia Polarization

Cui

Tang

et al. 2023

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose This study aimed to investigate the age-dependent anti-angiogenic capability of melatonin in choroidal neovascularization (CNV) and to explore the underlying molecular mechanisms. Methods In the present study, a laser-induced CNV model was established in both young (three months of age) and old (18 months of age) mice, and the size of CNV lesions and vascular leakage was detected by morphological and imaging examination. Next, Western blot and immunostaining were used to observe the levels of M2 markers, senescence-related markers, and molecules involved in IL-10/STAT3 pathway. Additionally, colivelin was used to study the effect of IL-10/STAT3 pathway activation on the expression of M2 markers and senescence-related markers by Western blot and immunostaining. Finally, the effects of colivelin on melatonin-induced reduction of CNV size and vascular leakage in mice at different ages were assessed using morphological and imaging examination. Results Our results revealed that aging promoted M2 macrophage/microglia polarization, and aggravated CNV and vascular leakage. Melatonin significantly inhibited the M2 polarization of senescent macrophage/microglia and reduced the CNV area and vascular leakage. Moreover, melatonin markedly suppressed IL-10/STAT3 pathway activation in the macrophage/microglia of old mice, and STAT3 activator colivelin reversed the suppressive effect of melatonin on M2 polarization of senescent macrophage/microglia and laser-induced CNV in old mice. Conclusions Our data demonstrated that melatonin significantly prevented the M2 polarization of senescent macrophage/microglia by inhibiting the IL-10/STAT3 pathway, and eventually attenuated senescence-associated CNV. These findings suggested that melatonin could serve as a promising therapeutic agent to treat CNV and other age-related ocular diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Therapeutic Benefit of Melatonin in Choroidal Neovascularization During Aging Through the Regulation of Senescent Macrophage/Microglia Polarization

Cui

Tang

et al. 2023

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…The Beaver Dam study found that patients with mild drusen had a significantly higher chance of progressing to more severe stages of AMD [3].…”

Section: Resultsmentioning

confidence: 99%

The modern view of the state of the problem of age-macular degeneration, its connection with genetics

Saldan

2023

SR:MS

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is now recognized as a complex genetic condition in which any number of genes influence a person's susceptibility to developing the disorder. Earlier studies of genetics, in addition to population-based genetic epidemiologic approaches, strongly emphasized the importance of genetics in AMD. Although the degree of heritability and the number of genes are related, the behavioural and genetic variability of the disease remains unclear, but access to modern diagnostic methods, ophthalmological and molecular genetics, expands our understanding of the mechanisms of its development and progression. One of the main problems of ophthalmological research in the coming years will be to determine the genetic cause of AMD. The use of various genetic methods provides the best chance of determining the function of one or more genes in the pathophysiology of this condition. The aim of this article is to conduct an analysis of the current literature to understand the pathogenesis of AMD at the molecular level and to provide the opportunity to establish and investigate new treatment methods, as well as to provide a treatment strategy that combines nutritional, environmental, and pharmacological methods to reduce the effect of genetic susceptibility and preserve vision. Materials and methods - sources of information in the form of scientific articles, research works and monographs were selected for the analytical review of the literature. Databases such as PubMed, Google Scholar, Scopus and Web Of Science were used. Research results - in the analytical review of modern domestic and foreign literature, it was determined that the use of various genetic methods provides the best chances to determine the function of one or more genes in the pathophysiology of age-related macular degeneration. Conclusions - one of the main problems of ophthalmological research in the coming years will be to determine the genetic cause of AMD. The use of various genetic methods provides the best chance of determining the function of one or more genes in the pathophysiology of this condition. The goals are to identify people at high risk of developing AMD before they develop symptoms or serious pathology, to understand the pathogenesis of AMD at the molecular level and to enable the establishment and investigation of new treatments, as well as to provide a treatment strategy that combines nutritional, environmental, and pharmacological methods to reduce the effect of genetic susceptibility and preserve vision

show abstract

“…A clinical study using donated eyes from AMD patients found that microglia accumulate in the subretinal space with a rather amoeboid, activated morphology, and display engulfed melanin or spontaneous fluorescent particles [ 83 ]. These amoeboid like microglia can affect the RPE-Bruch’s membrane, and cause pigmentation abnormalities [ 84 ]. The interaction between microglia and RPE cells causes the disruption of the outer blood retinal barrier (BRB) with the amplified recruitment of microglial cells by RPE-derived IL-6 [ 85 ].…”

Section: Molecular Mechanisms Of Microglia Involvement In Amdmentioning

confidence: 99%

Crosstalk Between Microglia and Müller Glia in the Age-Related Macular Degeneration: Role and Therapeutic Value of Neuroinflammation

2024

Aging dis

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is a progressive neurodegeneration disease that causes photoreceptor demise and vision impairments. In AMD pathogenesis, the primary death of retinal neurons always leads to the activation of resident microglia. The migration of activated microglia to the ongoing retinal lesion and their morphological transformation from branching to ameboid-like are recognized as hallmarks of AMD pathogenesis. Activated microglia send signals to Müller cells and promote them to react correspondingly to damaging stimulus. Müller cells are a type of neuroglia cells that maintain the normal function of retinal neurons, modulating innate inflammatory responses, and stabilize retinal structure. Activated Müller cells can accelerate the progression of AMD by damaging neurons and blood vessels. Therefore, the crosstalk between microglia and Müller cells plays a homeostatic role in maintaining the retinal environment, and this interaction is complicatedly modulated. In particular, the mechanism of mutual regulation between the two glia populations is complex under pathological conditions. This paper reviews recent findings on the crosstalk between microglia and Müller glia during AMD pathology process, with special emphasis on its therapeutic potentials.

show abstract

Interplay between aging and other factors of the pathogenesis of age-related macular degeneration

Cited by 38 publications

References 220 publications

Therapeutic Benefit of Melatonin in Choroidal Neovascularization During Aging Through the Regulation of Senescent Macrophage/Microglia Polarization

Therapeutic Benefit of Melatonin in Choroidal Neovascularization During Aging Through the Regulation of Senescent Macrophage/Microglia Polarization

The modern view of the state of the problem of age-macular degeneration, its connection with genetics

Crosstalk Between Microglia and Müller Glia in the Age-Related Macular Degeneration: Role and Therapeutic Value of Neuroinflammation

Contact Info

Product

Resources

About