Innate immune biology in age-related macular degeneration

Ascunce, Karina; Dhodapkar, Rahul; Huang, Deven; Hafler, Brian P.

doi:10.3389/fcell.2023.1118524

Cited by 10 publications

(6 citation statements)

References 65 publications

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“…A well-orchestrated, adequately replenished inflammatory response is required in such a pathological scenario to deliver protection from further damage and to ensure that functionality and structure are restored in the affected tissues [40]. When the exhausted immune cells and overwhelmed local reparative functions that occur in AMD fail to mediate a successful controlled inflammatory response, this culminates in advancing stages of AMD and progressive loss of vision [49,50].…”

Section: Immunosenescencementioning

confidence: 99%

Immune System, Inflammation and Autoantigens in Wet Age-Related Macular Degeneration: Pathological Significance and Therapeutic Importance

Manikandan,

Logan,

Cerrada-Gimenez

et al. 2023

Life

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Wet age-related macular degeneration (wAMD) is a chronic inflammation-associated neurodegenerative disease affecting the posterior part of the eye in the aging population. Aging results in the reduced functionality of cells and tissues, including the cells of the retina. Initiators of a chronic inflammatory and pathologic state in wAMD may be a result of the accumulation of inevitable metabolic injuries associated with the maintenance of tissue homeostasis from a young age to over 50. Apart from this, risk factors like smoking, genetic predisposition, and failure to repair the injuries that occur, alongside attempts to rescue the hypoxic outer retina may also contribute to the pathogenesis. Aging of the immune system (immunosenescence) and a compromised outer blood retinal barrier (BRB) result in the exposure of the privileged milieu of the retina to the systemic immune system, further increasing the severity of the disease. When immune-privileged sites like the retina are under pathological stress, certain age- and disease-related conditions may necessitate assistance from cells distant from the resident ones to help restore the functionality of the tissue. As a necessary part of tissue repair, inflammation is a major response to disease and recruits immune cells to the site of damage. We suspect that the specific reparative inflammatory responses are controlled by an autoantigen-T cell-mediated mechanism, a process that may be hindered in wAMD.

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Section: Immunosenescencementioning

confidence: 99%

Immune System, Inflammation and Autoantigens in Wet Age-Related Macular Degeneration: Pathological Significance and Therapeutic Importance

Manikandan,

Logan,

Cerrada-Gimenez

et al. 2023

Life

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“…There is growing evidence that one possible factor involved in the pathogenesis and progression of AMD is autoimmunity against retinal antigens and inflammatory reactions dependent on complement system activation [16][17][18][19]. In the aging process, chronic inflammation, known as para-inflammation or inflammaging, is believed to be an adaptive response of the immune system to increased oxidative stress and noxious insults so as to maintain local tissue homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Circulating Anti-Endothelial Cell Antibodies in Patients with Geographic Atrophy Related to Dry Age-Related Macular Degeneration

Żuber-Łaskawiec,

Wilańska,

Karska-Basta

et al. 2024

Medicina

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Background and Objectives: Age-related macular degeneration (AMD) is one of the leading causes of central vision loss among elderly patients, and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As inflammation and immune system involvement are strongly suggested to play a central role in promoting the degenerative process and stimulating the onset of complications, we aimed to analyze the frequency of serum anti-retinal (ARAs) and anti-endothelial cell antibodies (AECAs) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably the area of geographic atrophy (GA). Materials and Methods: This study included 41 patients with advanced-stage dry AMD and 50 healthy controls without AMD, matched for gender and age. ARAs were detected by indirect immunofluorescence using monkey retina as an antigen substrate, and the presence of AECAs was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARAs were detected in 36 (87.8%) AMD patients (titers ranged from 1:20 to 1:320) and in 16 (39.0%) (titers ranged from 1:10 to 1:40) controls (p = 0.0000). Twenty of the forty-one patients (48.8%) were positive for AECAs, while in the control group, AECAs were present only in five sera (10.0%). The titers of AECAs in AMD patients ranged from 1:100 to 1:1000, and in the control group, the AECA titers were 1:100 (p = 0.0001). There were no significant correlations between the presence of AECAs and disease activity. Conclusions: This study demonstrates a higher prevalence of circulating AECAs in patients with dry AMD; however, no correlation was found between the serum levels of these autoantibodies and the area of GA.

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“…The maintenance of retinal function is critically dependent on the normal functioning of the blood-retinal barrier (Kaur et al, 2008;O'Leary and Campbell, 2023). Fundus diseases and related systematic diseases can cause functional changes in the fundus such as ischemia and hypoxia, which can damage the bloodretinal barrier, leading to retinal vascular permeability changes, hemorrhage, exudation, neovascularization, and other lesions (Pournaras et al, 2008;Ascunce et al, 2023;Monickaraj et al, 2023). Diabetes mellitus (DM) is a common endocrine metabolic disease with its microvascular complications in the eye that can result in diabetic retinopathy (DR), which is the leading cause of blindness in working-age people (Bourne et al, 2021;Steinmetz et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Artificial Intelligence Applications in Chronic Ocular Diseases

2024

Frontiers Research Topics

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Innate immune biology in age-related macular degeneration

Cited by 10 publications

References 65 publications

Immune System, Inflammation and Autoantigens in Wet Age-Related Macular Degeneration: Pathological Significance and Therapeutic Importance

Immune System, Inflammation and Autoantigens in Wet Age-Related Macular Degeneration: Pathological Significance and Therapeutic Importance

Circulating Anti-Endothelial Cell Antibodies in Patients with Geographic Atrophy Related to Dry Age-Related Macular Degeneration

Artificial Intelligence Applications in Chronic Ocular Diseases

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