PURPOSE. Laminin N-terminus (LaNt) a31 is a relatively unstudied protein derived from the laminin a3 gene but structurally similar to netrins. LaNt a31 has, to date, been investigated only in two-dimensional (2D) keratinocyte culture where it influences cell migration and adhesion, processes integral to wound repair. Here we investigated LaNt a31 distribution in ocular surface epithelium, during limbal stem cell activation, and corneal wound healing.METHODS. Human, mouse, and pig eyes, ex vivo limbal explant cultures, and alkali burn wounds were processed for immunohistochemistry with antibodies against LaNt a31 along with progenitor cell-associated proteins. LaNt a31 expression was induced via adenoviral transduction into primary epithelial cells isolated from limbal explants, and cell spreading and migration were analyzed using live imaging.RESULTS. LaNt a31 localized to the basal layer of the conjunctival, limbal, and corneal epithelial cells. However, staining was nonuniform with apparent subpopulation enrichment, and some suprabasal reactivity was also noted. This LaNt a31 distribution largely matched that of keratin 15, epidermal growth factor receptor, and transformation-related protein 63a (p63a), and displayed similar increases in expression in activated limbal explants. During active alkali burn wound repair, LaNt a31 displayed increased expression in limbal regions and loss of basal restriction within the cornea. Distribution returned to predominately basal cell restricted once the wounded epithelium matured. Cultured corneal epithelial cells expressing LaNt a31 displayed increased 2D area and reduced migration, suggesting a functional link between this protein and key wound repair activities.CONCLUSIONS. These data place LaNt a31 in position to influence laminin-dependent processes including wound repair and stem cell activation.

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Disease of the cornea is the third leading cause of blindness worldwide. Corneal graft surgery is one of the most successful forms of solid organ transplantations in humans, with ever-increasing developments in surgical technique. To date, approximately 4504 corneal transplants are performed in the United Kingdom each year. While full thickness transplantation was the most commonly performed keratoplasty over the last few decades, selective lamellar transplantation of the diseased layers of the cornea has been universally adopted. This comprehensive review aims to provide an updated synthesis on different types of corneal transplantations, their treatment outcomes, and the associated complications of each procedure in both adult and paediatric population. In addition, we also present an up-to-date summary of the emerging therapeutic approaches that have the potential to reduce the demand for donor-dependent keratoplasty.

Unlike other types of breast cancer, triple negative breast cancer (TNBC) does not respond to therapies targeting human epidermal growth factor receptor-2 (HER2) or hormone therapy, and the prognosis of patients with TNBC is usually poor. The role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 10 (SNHG10) has been investigated in many types of cancer, but its role in TNBC is unknown. This study aimed to explore the role of SNHG10 in TNBC in the context of doxorubicin treatment, a common therapy for TNBC. Analysis of the TCGA dataset revealed the downregulation of SNHG10 in TNBC. The downregulation of SNHG10 of TNBC in TNBC was further confirmed by detecting its expression in 60 patients with TNBC by qPCR. The expression of SNHG10 was further downregulated after doxorubicin treatment. In TNBC, microRNA-302b (miR-302b) was downregulated and was positively correlated with SNHG10. In TNBC cells, overexpression of SNHG10 resulted in upregulation of miR-302b, and methylation-specific PCR analysis showed that SNHG10 negatively regulates the methylation of miR-302b. In addition, doxorubicin treatment resulted in the downregulation of SNHG10 in TNBC cells, and overexpression of SNHG10 and miR-302b promoted apoptosis of doxorubicin-treated TNBC cells. Furthermore, overexpression of both SNHG10 and miR-302b had a stronger effect on apoptosis than that of overexpression of SNHG10 alone. Our study showed that SNHG10 could inhibit the development of resistance to doxorubicin by upregulating miR-302b in TNBC through methylation. Our findings suggested that SNHG10 might serve as a molecular target for intervening in TBNC metastasis.