Role of Serine Protease Inhibitors A1 and A3 in Ocular Pathologies.

Serine protease inhibitors A1 (SerpinA1) and A3 (SerpinA3) are important members of the serpin family, playing crucial roles in the regulation of serine proteases and influencing various physiological processes. SerpinA1, also known as α-1-antitrypsin, is a versatile glycoprotein predominantly synthesized in the liver, with additional production in inflammatory and epithelial cell types. It exhibits multifaceted functions, including immune modulation, complement activation regulation, and inhibition of endothelial cell apoptosis. SerpinA3, also known as α-1-antichymotrypsin, is expressed both extracellularly and intracellularly in various tissues, particularly in the retina, kidney, liver, and pancreas. It exerts anti-inflammatory, anti-angiogenic, antioxidant, and antifibrotic activities. Both SerpinA1 and SerpinA3 have been implicated in conditions such as keratitis, diabetic retinopathy, age-related macular degeneration, glaucoma, cataracts, dry eye disease, keratoconus, uveitis, and pterygium. Their role in influencing metalloproteinases and cytokines, as well as endothelial permeability, and their protective effects on Müller cells against oxidative stress further highlight their diverse and critical roles in ocular pathologies. This review provides a comprehensive overview of the etiology and functions of SerpinA1 and SerpinA3 in ocular diseases, emphasizing their multifaceted roles and the complexity of their interactions within the ocular microenvironment.

Blockade of interleukin-6 trans-signaling prevents mitochondrial dysfunction and cellular senescence in retinal endothelial cells.

Interleukin-6 (IL-6) is a multifaceted cytokine implicated in the pathogenesis of diabetic retinopathy (DR). Its activity extends through cis- and trans-signaling (TS) pathways, with cis-signaling limited to specific cell types possessing the membrane-bound IL-6 receptor, while trans-signaling broadly activates various cells without the membrane bound IL-6 receptor, including retinal endothelial cells. In this study, we determined the effects of interleukin-6 trans-signaling on mitochondrial dysfunction and cellular senescence in human retinal endothelial cells (HRECs). HRECs were cultured and treated with IL-6 + soluble IL-6R or Hyper IL-6 to activate trans-signaling, along with sgp130Fc for inhibition. RT-PCR was used to analyze gene expression changes associated with inflammation and senescence. Cellular senescence was assessed using SA ß-gal staining. Mitochondrial function was evaluated using Seahorse XFe24 Bioanalyzer. IL-6 trans-signaling induced inflammatory gene expression as indicated by the upregulation of ICAM1, MCP1, and SERPINA3 levels. Additionally, it reduced mitochondrial respiration and oxidative phosphorylation, and these effects were counteracted by sgp130Fc. Moreover, IL-6 trans-signaling led to altered expression of apoptosis-associated genes, including downregulation of FIS1, BCL2, and MCL1, while promoting cellular senescence, a phenomenon mitigated by sgp130Fc. These results not only deepen our understanding of IL-6 in DR but also carry broader implications for age-related diseases and the aging process itself. This study underscores the potential therapeutic value of targeting IL-6 trans-signaling with sgp130Fc as a promising anti-inflammatory approach for DR and potentially other inflammatory conditions. Further in-vivo investigations are warranted to elucidate the function of IL-6 trans-signaling in aging-related pathologies and overall organismal health.

Understanding Acquired Brain Injury: A Review.

Any type of brain injury that transpires post-birth is referred to as Acquired Brain Injury (ABI). In general, ABI does not result from congenital disorders, degenerative diseases, or by brain trauma at birth. Although the human brain is protected from the external world by layers of tissues and bone, floating in nutrient-rich cerebrospinal fluid (CSF); it remains susceptible to harm and impairment. Brain damage resulting from ABI leads to changes in the normal neuronal tissue activity and/or structure in one or multiple areas of the brain, which can often affect normal brain functions. Impairment sustained from an ABI can last anywhere from days to a lifetime depending on the severity of the injury; however, many patients face trouble integrating themselves back into the community due to possible psychological and physiological outcomes. In this review, we discuss ABI pathologies, their types, and cellular mechanisms and summarize the therapeutic approaches for a better understanding of the subject and to create awareness among the public.