Complement System and Age-Related Macular Degeneration: Implications of Gene-Environment Interaction for Preventive and Personalized Medicine

Maugeri, Andrea; Barchitta, Martina; Mazzone, Maria Grazia; Giuliano, Francesco; Agodi, Antonella

doi:10.1155/2018/7532507

Cited by 29 publications

(23 citation statements)

References 178 publications

(171 reference statements)

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“…Complement components are organized in hierarchal proteolytic cascades and represent the first defense‐line of the organism. [ 29 ] The complement system also modulates various physiological activities of the body such as: i) the host defense against pathogenic infections through various strategies (e.g., opsonization, chemotaxis, and leukocytes activation; lysis of bacteria and cell membranes); ii) the natural innate and adaptive immunity; iii) the clearance of immune complex and apoptotic cells from body tissues. [ 30 ]…”

Section: Complement System Activationmentioning

confidence: 99%

Immunogenicity of Polyethylene Glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach

d’Avanzo

Celia

Barone

et al. 2020

Advanced Therapeutics

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PEGylation technique is currently considered the gold standard approach to provide a long and safe circulation of drugs. Although this is the accepted dogma, various clinical reports and animal studies show the occurrence of immunogenic responses against polyethylene glycol (PEG) after systemic injection. These side effects, associated with complement activation and/or anti‐PEG antibody production, result in hypersensitivity reactions and lack of therapeutic efficacy of the drug during clinical protocols. Furthermore, different healthy patients show the presence of anti‐PEG antibodies in their blood stream, even though they have not received PEGylated drugs. The aim of this review is to discuss the main mechanisms based on PEG immunogenicity and its clinical implications and report the most promising approaches to reduce these unexpected side effects.

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Section: Complement System Activationmentioning

confidence: 99%

Immunogenicity of Polyethylene Glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach

d’Avanzo

Celia

Barone

et al. 2020

Advanced Therapeutics

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“…All the three signaling led to the cleavage of C3 central component and to formation of the terminal lytic/pro-inflammatory membrane attack complex (MAC) on infected or damaged target cells [109]. In the elderly, besides renal disease, aberrant complement activation is involved in the physiopathology of several conditions such as Alzheimer's disease [110], Amyotrophic lateral sclerosis, multiple sclerosis or age-related macular degeneration [111]. Interestingly, the classical pathway initiator C1q level increases with aging and can activate Wnt/β-catenin signaling that is involved in the skeletal muscle aging.…”

Section: Complement System In the Elderlymentioning

confidence: 99%

Molecular Mechanisms of AKI in the Elderly: From Animal Models to Therapeutic Intervention

Infante

Franzin

Madio

et al. 2020

JCM

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Acute kidney injury (AKI), a critical syndrome characterized by a sudden reduction of renal function, is a common disorder among elderly patients particularly in Intensive Care Unit (ICU). AKI is closely associated with both short- and long-term mortality and length of hospital stay and is considered a predictor of chronic kidney disease (CKD). Specific hemodynamic, metabolic, and molecular changes lead to increased susceptibility to injury in the aged kidney; therefore, certain causes of AKI such as the prerenal reduction in renal perfusion or vascular obstructive conditions are more common in the elderly; moreover, AKI is often multifactorial and iatrogenic. Older patients present several comorbidities (diabetes, hypertension, heart failure) and are exposed to multiple medical interventions such as the use of nephrotoxic contrasts media and medications, which can also trigger AKI. Considering the emerging relevance of this condition, prevention and treatment of AKI in the elderly should be crucial in the internist and emergency setting. This review article summarizes the incidence, the risk factors, the pathophysiology, the molecular mechanisms and the strategies of prevention and treatment of AKI in elderly patients.

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“…Among them, the scores are general high, and eight genes are members in complement system. In addition, researchers have focused on the complement pathways involved in AMD and their preventive/personalized medicine correspondingly [52,53].…”

Section: Discussionmentioning

confidence: 99%

Complement family member CFI polymorphisms and AMD susceptibility from a comprehensive analysis

2020

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The complement factor I (CFI) gene polymorphisms have been reported to age-related macular degenerative (AMD) risk, nevertheless, above association is not consistent. We investigated a meta-analysis to evaluate the conclusions between CFI polymorphisms (rs10033900 and rs2285714) and AMD risk. An identification was covered with the PubMed and other databases through February 8, 2020. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of associations. After a comprehensive search, 11 different articles (12 case–control studies for total AMD and 11 case–control studies about neovascular disease/geographic atrophy in AMD) were retrieved. Individuals carrying C-allele or CC genotype of rs10033900 polymorphism may have a decreased risk to be AMD disease. For example, there has a significantly decreased relationship between rs10033900 polymorphism and AMD both in the whole group, Caucasian population and population-based source of control. Moreover, a similar trend in subgroup of genotype method group by MALDI-TOF MS was detected. To classify the type of AMD in further, decreased association was also observed in both neovascular disease and geographic atrophy AMD. No association was found about rs2285714 polymorphism. Our present groundbreaking study suggests that the CFI rs10033900 polymorphism is potentially associated with the risk of AMD development.

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Complement System and Age-Related Macular Degeneration: Implications of Gene-Environment Interaction for Preventive and Personalized Medicine

Cited by 29 publications

References 178 publications

Immunogenicity of Polyethylene Glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach

Immunogenicity of Polyethylene Glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach

Molecular Mechanisms of AKI in the Elderly: From Animal Models to Therapeutic Intervention

Complement family member CFI polymorphisms and AMD susceptibility from a comprehensive analysis

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