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Dry eye disease (DED) is a widespread ophthalmic illness that inflicts massive economic and medical burdens on society. Although oxidative stress is closely associated with the onset of DED, barely any quantities of antioxidants are clinically available owing to low efficiency, toxicity, and poor bioavailability. Cerium‐based nanozymes possess promising enzyme‐mimetic activities in scavenging reactive oxygen species (ROS). Moreover, the ultra‐small metal–organic frameworks (MOFs) have the potential for more efficient drug delivery, ROS elimination, and therapeutic efficacy. However, the development of ultra‐small cerium‐based MOFs (Ce‐MOFs) is limited to a small minority due to challenges in the synthetic process and stability. By simply adjusting raw ingredients concentrations, three types of Ce‐MOFs with distinct particle sizes are synthesized: Ce‐MOF 1 (213 nm), Ce‐MOF 2 (36 nm), and Ce‐MOF 3 (2 nm). In comparison, the obtained ultra‐small Ce‐MOF 3 exhibited superior ROS scavenging and antioxidant capacity, decreased cytotoxicity, and excellent ocular penetration. Therapeutically, Ce‐MOF 3 is demonstrated to be highly efficient in alleviating DED by suppressing oxidative stress and inflammation, boosting corneal epithelial repair, and facilitating tear secretion recovery. The novel ultra‐small Ce‐MOF 3 may serve as a promising alternative treatment for DED and other ROS‐related disorders when combined with ocular biocompatibility. [ABSTRACT FROM AUTHOR]

Ferroptosis, characterized by glutamate overload, glutathione depletion, and cysteine/cystine deprivation during iron- and oxidative-damage-dependent cell death, is a particular mode of regulated cell death. It is expected to effectively treat cancer through its tumor-suppressor function, as mitochondria are the intracellular energy factory and a binding site of reactive oxygen species production, closely related to ferroptosis. This review summarizes relevant research on the mechanisms of ferroptosis, highlights mitochondria's role in it, and collects and classifies the inducers of ferroptosis. A deeper understanding of the relationship between ferroptosis and mitochondrial function may provide new strategies for tumor treatment and drug development based on ferroptosis. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the protective effect of melatonin on the corneal epithelium in dry eye disease(DED) and explore its underlying mechanism. Human corneal epithelial(HCE) cells was exposure to t-butylhydroperoxide(tBH), C57BL/6 mice were injected of subcutaneous scopolamine to imitate DED. Melatonin was used both in vivo and in vitro. Cell viability was detected by Cell Counting Kit-8 assay and Lactate Dehydrogenase Leakage. The change of cellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and apoptosis was analyzed by flow cytometry. Western blot assays and immunofluorescence were carried out to measure protein changes. mRNA expression was investigated by RNA sequencing (RNA-Seq) and quantitative real-time PCR. The change of autophagic flux were observed through mCherry-GFP-LC3 transfection and electron microscopy(TEM). Clinical parameters of corneal epithelium defects, conjunctival goblet cells, tear volume, and level of ocular surface inflammation was recorded. Melatonin was able to reduce excessive ROS production and maintain mitochondrial function. TEM assay found melatonin rescued impaired autophagic flux under tBH. Moreover, melatonin significantly preserved cell viability, abolished LDH release, and decreased apoptosis. RNA-Seq indicated that melatonin greatly activating hemeoxygenase-1 (HO-1) expression. Interestingly, HO-1 ablation largely attenuated its protective effects. Besides, in dry eye mouse model, intraperitoneal injection of melatonin showed greatly improved clinical parameters, inhibited activated NLRP3 inflammation cascade, and increased density of goblet cells and tear volume. Thus, melatonin protects corneal epithelial cells from oxidative damage, maintain normal level of autophagy, and reduce inflammation via trigging HO-1 expression in DED. • Melatonin can protect corneal epithelial cell viability and inhibit apoptosis from oxidative damage in vitro. • Melatonin maintains healthy autophagic flux, reduces ROS level via trigging HO-1 expression. • melatonin in vivo greatly protected ocular surface and inhibited inflammation activation. [ABSTRACT FROM AUTHOR]