Multifaceted mitochondrial as a novel therapeutic target in dry eye: insights and interventions.

Dry eye, recognized as the most prevalent ocular surface disorder, has risen to prominence as a significant public health issue, adversely impacting the quality of life for individuals across the globe. Despite decades of extensive research into the chronic inflammation that characterizes dry eye, the intricate mechanisms fueling this persistent inflammatory state remain incompletely understood. Among the various cellular components under investigation, mitochondria-essential for cellular energy production and homeostasis-have attracted increasing attention for their role in dry eye pathogenesis. This involvement points to mechanisms such as oxidative stress, apoptosis, and sustained inflammation, which are central to the progression of the disease. This review aims to provide a thorough exploration of mitochondrial dysfunction in dry eye, shedding light on the critical roles played by mitochondrial oxidative stress, apoptosis, and mitochondrial DNA damage. It delves into the mechanisms through which diverse pathogenic factors may trigger mitochondrial dysfunction, thereby contributing to the onset and exacerbation of dry eye. Furthermore, it lays the groundwork for an overview of current therapeutic strategies that specifically target mitochondrial dysfunction, underscoring their potential in managing this complex condition. By spotlighting this burgeoning area of research, our review seeks to catalyze the development of innovative drug discovery and therapeutic approaches. The ultimate goal is to unlock promising avenues for the future management of dry eye, potentially revolutionizing treatment paradigms and improving patient outcomes. Through this comprehensive examination, we endeavor to enrich the scientific community's understanding of dry eye and inspire novel interventions that address the underlying mitochondrial dysfunctions contributing to this widespread disorder.

Ouyang W ，Yan D ，Hu J ，Liu Z ... -  《Cell Death Discovery》

Comprehensive dry eye therapy: overcoming ocular surface barrier and combating inflammation, oxidation, and mitochondrial damage.

Dry Eye Disease (DED) is a prevalent multifactorial ocular disease characterized by a vicious cycle of inflammation, oxidative stress, and mitochondrial dysfunction on the ocular surface, all of which lead to DED deterioration and impair the patients' quality of life and social functioning. Currently, anti-inflammatory drugs have shown promising efficacy in treating DED; however, such drugs are associated with side effects. The bioavailability of ocular drugs is less than 5% owing to factors such as rapid tear turnover and the presence of the corneal barrier. This calls for investigations to overcome these challenges associated with ocular drug administration. A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study. In terms of delivery, PHP-DPS@INS nanoparticles (NPs) overcame the ocular surface transport barrier by adopting the strategy of "ocular surface electrostatic adhesion-lysosomal site-directed escape". In terms of therapy, PHP-DPS@INS achieved mitochondrial targeting and antioxidant effects through SS-31 peptide, and exerted an anti-inflammatory effect by loading insulin to reduce mitochondrial inflammatory metabolites. Ultimately, the synergistic action of "anti-inflammation-antioxidation-mitochondrial function restoration" breaks the vicious cycle associated with DED. The PHP-DPS@INS demonstrated remarkable cellular uptake, lysosomal escape, and mitochondrial targeting in vitro. Targeted metabolomics analysis revealed that PHP-DPS@INS effectively normalized the elevated level of mitochondrial proinflammatory metabolite fumarate in an in vitro hypertonic model of DED, thereby reducing the levels of key inflammatory factors (IL-1β, IL-6, and TNF-α). Additionally, PHP-DPS@INS strongly inhibited reactive oxygen species (ROS) production and facilitated mitochondrial structural repair. In vivo, the PHP-DPS@INS treatment significantly enhanced the adhesion duration and corneal permeability of the ocular surface in DED mice, thereby improving insulin bioavailability. It also restored tear secretion, suppressed ocular surface damage, and reduced inflammation in DED mice. Moreover, it demonstrated favorable safety profiles both in vitro and in vivo. In summary, this study successfully developed a comprehensive DED management nanosystem that overcame the ocular surface transmission barrier and disrupted the vicious cycle that lead to dry eye pathogenesis. Additionally, it pioneered the regulation of mitochondrial metabolites as an anti-inflammatory treatment for ocular conditions, presenting a safe, efficient, and innovative therapeutic strategy for DED and other inflammatory diseases.

Xia Y ，Zhang Y ，Du Y ，Wang Z ，Cheng L ，Du Z ... -  《JOURNAL OF NANOBIOTECHNOLOGY》

Potential New Target for Dry Eye Disease-Oxidative Stress.

Bu J ，Liu Y ，Zhang R ，Lin S ，Zhuang J ，Sun L ，Zhang L ，He H ，Zong R ，Wu Y ，Li W ... -  《Antioxidants》

Mitochondrial biogenesis: pharmacological approaches.

Valero T 《-》

Mitochondrial Dysfunction in Chronic Obstructive Pulmonary Disease: Unraveling the Molecular Nexus.

Li CL ，Liu JF ，Liu SF 《Biomedicines》