The Role of Inflammation and Infection in Age-Related Neurodegenerative Diseases: Lessons From Bacterial Meningitis Applied to Alzheimer Disease and Age-Related Macular Degeneration

Age-related neurodegenerative diseases, such as Alzheimer disease (AD) and age-related macular degeneration (AMD), are multifactorial and have diverse genetic and environmental risk factors. Despite the complex nature of the diseases, there is long-standing, and growing, evidence linking microbial infection to the development of AD dementia, which we summarize in this article. Also, we highlight emerging research findings that support a role for parainfection in the pathophysiology of AMD, a disease of the neurosensory retina that has been shown to share risk factors and pathological features with AD. Acute neurological infections, such as Bacterial Meningitis (BM), trigger inflammatory events that permanently change how the brain functions, leading to lasting cognitive impairment. Neuroinflammation likewise is a known pathological event that occurs in the early stages of chronic age-related neurodegenerative diseases AD and AMD and might be triggered as a parainfectious event. To date, at least 16 microbial pathogens have been linked to the development of AD; on the other hand, investigation of a microbe-AMD relationship is in its infancy. This mini-review article provides a synthesis of existing evidence indicating a contribution of parainfection in the aetiology of AD and of emerging findings that support a similar process in AMD. Subsequently, it describes the major immunopathological mechanisms that are common to BM and AD/AMD. Together, this evidence leads to our proposal that both AD and AMD may have an infectious aetiology that operates through a dysregulated inflammatory response, leading to deleterious outcomes. Last, it draws fresh insights from the existing literature about potential therapeutic options for BM that might alleviate neurological disruption associated with infections, and which could, by extension, be explored in the context of AD and AMD.

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Incidence of elevated intraocular pressure after intravitreal injection in Japanese patients with age-related macular degeneration

Scientific Reports ◽

10.1038/s41598-021-91832-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maiko Maruyama-Inoue ◽

Tatsuya Inoue ◽

Shaheeda Mohamed ◽

Yoko Kitajima ◽

Shoko Ikeda ◽

...

Keyword(s):

Risk Factors ◽

Intraocular Pressure ◽

Macular Degeneration ◽

Intravitreal Injection ◽

Odds Ratio ◽

Japanese Patients ◽

Age Related Macular Degeneration ◽

Age Related ◽

Elevated Intraocular Pressure ◽

History Of

AbstractThe purpose of this study was to report the incidence of elevated intraocular pressure (IOP) after intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) in Japanese patients with age-related macular degeneration (AMD). A retrospective study of chart review of patients who underwent ≥ 10 intravitreal anti-VEGF injections between April 2009 and December 2019 was conducted. Elevated IOP was defined as IOP ≥ 25 mmHg at one visit. Cases with elevated IOP resulting from IVI were identified. Furthermore, the association between elevated IOP and some parameters, as the risk factors that influence elevated IOP, was investigated. A total of 402 eyes of 370 patients were included in this study. Twenty-eight eyes of 26 patients (7.0%) were identified as cases with elevated IOP after IVI. The mean time of elevation after baseline was 50.6 ± 26.5 months. History of glaucoma (p = 0.021; odds ratio, 5.85), treatment modality (p = 0.019; odds ratio, 6.32), and total number of injections (p = 0.003; odds ratio, 1.03) were significantly associated with elevated IOP. A late complication of elevated IOP is associated with IVI in patients with AMD. Particularly, history of glaucoma and treat and extend regimen with frequent injections were found to be risk factors of elevated IOP.

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Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms22031170 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1170

Author(s):

Arunbalaji Pugazhendhi ◽

Margaret Hubbell ◽

Pooja Jairam ◽

Balamurali Ambati

Keyword(s):

Risk Factors ◽

Macular Degeneration ◽

Kinase Inhibitors ◽

Rho Kinase ◽

The Elderly ◽

Age Related Macular Degeneration ◽

Gene Therapies ◽

Rho Kinase Inhibitors ◽

Age Related ◽

Endothelial Growth Factor

Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. Risk factors such as age, race, genetics, iris color, smoking, drinking, BMI, and diet all play a part in nvAMD’s progression, with anti-vascular endothelial growth factor (anti-VEGF) therapy being the mainstay of treatment. Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. Newer therapies such as gene therapies, Rho-kinase inhibitors, and levodopa offer potential new targets for treatment.

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