Injectable, Antioxidative, and Tissue-Adhesive Nanocomposite Hydrogel as a Potential Treatment for Inner Retina Injuries.

Reactive oxygen species (ROS) have been recognized as prevalent contributors to the development of inner retinal injuries including optic neuropathies such as glaucoma, non-arteritic anterior ischemic optic neuropathy, traumatic optic neuropathy, and Leber hereditary optic neuropathy, among others. This underscores the pivotal significance of oxidative stress in the damage inflicted upon retinal tissue. To combat ROS-related challenges, this study focuses on creating an injectable and tissue-adhesive hydrogel with tailored antioxidant properties for retinal applications. GelCA, a gelatin-modified hydrogel with photo-crosslinkable and injectable properties, is developed. To enhance its antioxidant capabilities, curcumin-loaded polydopamine nanoparticles (Cur@PDA NPs) are incorporated into the GelCA matrix, resulting in a multifunctional nanocomposite hydrogel referred to as Cur@PDA@GelCA. This hydrogel exhibits excellent biocompatibility in both in vitro and in vivo assessments, along with enhanced tissue adhesion facilitated by NPs in an in vivo model. Importantly, Cur@PDA@GelCA demonstrates the potential to mitigate oxidative stress when administered via intravitreal injection in retinal injury models such as the optic nerve crush model. These findings underscore its promise in advancing retinal tissue engineering and providing an innovative strategy for acute neuroprotection in the context of inner retinal injuries.

The effect of resveratrol on protecting corneal epithelial cells from cytotoxicity caused by moxifloxacin and benzalkonium chloride.

PURPOSE: Moxifloxacin (MOX), a fourth generation fluoroquinolone (FQ), has a wide antibacterial spectrum, but may show cytotoxicity characterized by high productions of reactive oxygen species (ROS). This study investigated the protective role of a common antioxidant agent, resveratrol (trans-3,5,4'-trihydroxystilbene), against the cytotoxicity caused by MOX. METHODS: Experiments were performed with a human corneal epithelial cell line (HCECs; ATCC-CRL-11515). Another commonly used FQ, levofloxacin (LEV), and the most commonly used preservatives, benzalkonium chloride (BAC), were also used for comparison with MOX. Cell viability and morphologic changes after treatment were evaluated with trypan blue exclusion assay, propidium iodine/annexin V-FITC staining, and flow cytometry. Chemiluminescence immunoassay was used for ROS quantification. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, wound healing assay, and intracellular detections of oxidative stress were performed to evaluate the effects of resveratrol. RESULTS: The MOX group, similar to the BAC group, showed significant cell shrinkage and death compared with the LEV group. High ROS production in HCECs of MOX group was observed both by chemiluminescence immunoassay and intracellular images. Within the observations of MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay, live cell images, and wound healing process in vitro, the cytotoxic effects of the MOX and BAC groups were opposed by resveratrol. Human corneal epithelial cells pretreated with resveratrol demonstrated better cell viability and healing rate in the early stage. CONCLUSIONS: The protective effects of antioxidant agents indicate that MOX, similar to BAC, causes oxidative stress-related cell damage. The results also inspired us to think about a "supplementary regimen" to increase safety and decrease the adverse effect in the treatment of corneal infections.

Risk of skin cancer in patients with pterygium: a nationwide population-based cohort study in Taiwan.

This study investigated the association between pterygium and skin cancer linking to ultraviolet (UV) radiation using claims data from 1997-2010, obtained from the Taiwan National Health Insurance Research Database. The study included 19,701 patients with pterygium and 78,804 sex- and age-frequency-matched comparison subjects. Multivariate Cox regression analyses were performed to assess the relationship between pterygium and risk of skin cancer by the end of 2010. The incidence rates of malignant melanoma (MM) and nonmelanoma skin cancer (NMSC) in two cohorts and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of the diseases were measured. Results showed that the incidences of MM and NMSC were both higher in the pterygium cohort than in the comparison cohort (5.5 vs 3.2 and 32.3 vs 15.0 per 100,000 person years, respectively). After adjusting for age, sex, UV index, occupation, and the other comorbidities, pterygium remained a significant predictor of NMSC (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.11-2.42), but not MM (HR, 1.46; 95% CI, 0.59-3.65). These results suggest that pterygium patients are associated with an increased risk of NMSC, but not significant for MM.

Knockdown of zebrafish lumican gene (zlum) causes scleral thinning and increased size of scleral coats.

The lumican gene (lum), which encodes one of the major keratan sulfate proteoglycans (KSPGs) in the vertebrate cornea and sclera, has been linked to axial myopia in humans. In this study, we chose zebrafish (Danio rerio) as an animal model to elucidate the role of lumican in the development of axial myopia. The zebrafish lumican gene (zlum) spans approximately 4.6 kb of the zebrafish genome. Like human (hLUM) and mouse (mlum), zlum consists of three exons, two introns, and a TATA box-less promoter at the 5'-flanking region of the transcription initiation site. Sequence analysis of the cDNA predicts that zLum encodes 344 amino acids. zLum shares 51% amino acid sequence identity with human lumican. Similar to hLUM and mlum, zlum mRNA is expressed in the eye and many other tissues, such as brain, muscle, and liver as well. Transgenic zebrafish harboring an enhanced GFP reporter gene construct downstream of a 1.7-kb zlum 5'-flanking region displayed enhanced GFP expression in the cornea and sclera, as well as throughout the body. Down-regulation of zlum expression by antisense zlum morpholinos manifested ocular enlargement resembling axial myopia due to disruption of the collagen fibril arrangement in the sclera and resulted in scleral thinning. Administration of muscarinic receptor antagonists, e.g. atropine and pirenzepine, effectively subdued the ocular enlargement caused by morpholinos in in vivo zebrafish larvae assays. The observation suggests that zebrafish can be used as an in vivo model for screening compounds in treating myopia.