Senescent Cells: Dual Implications on the Retinal Vascular System.

Cellular senescence, a state of permanent cell cycle arrest in response to endogenous and exogenous stimuli, triggers a series of gradual alterations in structure, metabolism, and function, as well as inflammatory gene expression that nurtures a low-grade proinflammatory milieu in human tissue. A growing body of evidence indicates an accumulation of senescent neurons and blood vessels in response to stress and aging in the retina. Prolonged accumulation of senescent cells and long-term activation of stress signaling responses may lead to multiple chronic diseases, tissue dysfunction, and age-related pathologies by exposing neighboring cells to the heightened pathological senescence-associated secretory phenotype (SASP). However, the ultimate impacts of cellular senescence on the retinal vasculopathies and retinal vascular development remain ill-defined. In this review, we first summarize the molecular players and fundamental mechanisms driving cellular senescence, as well as the beneficial implications of senescent cells in driving vital physiological processes such as embryogenesis, wound healing, and tissue regeneration. Then, the dual implications of senescent cells on the growth, hemostasis, and remodeling of retinal blood vessels are described to document how senescent cells contribute to both retinal vascular development and the severity of proliferative retinopathies. Finally, we discuss the two main senotherapeutic strategies-senolytics and senomorphics-that are being considered to safely interfere with the detrimental effects of cellular senescence.

DNA methylation alterations in systemic lupus erythematosus: A systematic review of case-control studies.

BACKGROUND: Traditionally, the diagnosis and monitoring of disease activity in systemic lupus erythematosus (SLE) are contingent upon clinical manifestations and serological markers. However, researchers are struggling to find biomarkers with higher sensitivity and specificity. DNA methylation has been the most studied epigenetic feature in SLE. So, in this study, we performed a systematic review of studies about DNA methylation alterations in SLE patients compared to healthy controls. METHODS: By searching PubMed, Scopus, and Google Scholar up to July 2022, all case-control studies in which DNA methylation of specific genes was assessed by a non-high-throughput technique and passed the quality of bias assessment were included. RESULTS: In total, 44 eligible studies underwent a data extraction process. In all, 3471 SLE patients and 1028 healthy individuals were included. Among the studies that reported the patients' gender (n = 2853), 89.41% were female and 10.59% were male. Forty studies have been conducted on adult patients. The number of works on fractionated and unfractionated blood cells was almost equal. In this regard, 22 studies were conducted on whole blood or peripheral blood mononuclear cells and two studies on unfractionated white blood cells. Sorted blood cells were biological sources in 20 studies. The most investigated gene was IFI44L. Sensitivity, specificity, and diagnostic power of methylation levels were only reported for IFI44L in five studies. The most employed methylation profiling method was bisulfite sequencing polymerase chain reaction. The correlation between methylation patterns and clinical parameters was explored in 22 studies, which of them 16 publications displayed a remarkable association between DNA methylation status and clinical indices. CONCLUSIONS: The methylation status of some genes especially IFI44L, FOXP3, and MX1 has been suggested as promising SLE biomarkers. However, given the conflicting findings between studies because of potential confounders such as different sample types, methylation profiling methods, and ethnicity as well as shared DNA methylation patterns of SLE and other autoimmune diseases, DNA methylation biomarkers are currently not reliable diagnostic biomarkers and do not represent surrogate markers of SLE disease activity. Future investigations on a larger scale with the discarding of limitations of previous studies would probably lead to a consensus.