ABCB5 is a limbal stem cell gene required for corneal development and repair.

Corneal epithelial homeostasis and regeneration are sustained by limbal stem cells (LSCs), and LSC deficiency is a major cause of blindness worldwide. Transplantation is often the only therapeutic option available to patients with LSC deficiency. However, while transplant success depends foremost on LSC frequency within grafts, a gene allowing for prospective LSC enrichment has not been identified so far.

Lumican binds ALK5 to promote epithelium wound healing.

Lumican (Lum), a small leucine-rich proteoglycan (SLRP) family member, has multiple matricellular functions both as an extracellular matrix component and as a matrikine regulating cell proliferation, gene expression and wound healing. To date, no cell surface receptor has been identified to mediate the matrikine functions of Lum. This study aimed to identify a perspective receptor that mediates Lum effects on promoting wound healing.

Dexamethasone induces cross-linked actin networks in trabecular meshwork cells through noncanonical wnt signaling.

Purpose: Dexamethasone (DEX) regulates aqueous humor outflow by inducing a reorganization of the cytoskeleton to form cross-linked actin networks (CLANs) in trabecular meshwork (TM) cells. Rho-associated protein kinase (ROCK) has been demonstrated to have an important role in this process, but the upstream components leading to its activation remain elusive. The purpose of the study is to demonstrate that noncanonical Wnt signaling mediates the DEX-induced CLAN formation in TM cells.

Crosstalk between TGF-beta and MAPK signaling during corneal wound healing.

Purpose: The aim of this study was to elucidate the mechanisms governing epithelial cell migration and proliferation during wound healing.

Methods: The authors used wound healing of mouse corneal epithelium to examine the role TGF-β signaling plays during the healing process. To achieve this goal, they used transgenic mice in which the TGF-β receptor type II (Tbr2) was conditionally ablated from the corneal epithelium.

Clinical and histopathological features and immunoreactivity of human choroidal and ciliary melanomas as prognostic factors for metastasis and death.

Purposes: To determine the relationship between immunohistochemical reactivity to osteopontin, vimentin, keratin 8/18, LZTS1, and beta-catenin and clinical and histopathological prognostic factors for metastasis and death in archival specimens of primary uveal melanomas, and the prognostic value of the evaluated study variables for death from metastasis.

Methods: Retrospective analysis of clinical records and formalin-fixed, paraffin-embedded slides of primary uveal melanomas treated by enucleation during May 1 1999, through June 30 2009. Immunofluorescent staining of each tumor was assessed on newly prepared histologic slides after the application of antibodies directed against five biomarkers associated with unfavorable prognosis in uveal melanoma.

From hair to cornea: toward the therapeutic use of hair follicle-derived stem cells in the treatment of limbal stem cell deficiency.

Limbal stem cell deficiency (LSCD) leads to severe ocular surface abnormalities that can result in the loss of vision. The most successful therapy currently being used is transplantation of limbal epithelial cell sheets cultivated from a limbal biopsy obtained from the patient's healthy, contralateral eye or cadaveric tissue. In this study, we investigated the therapeutic potential of murine vibrissae hair follicle bulge-derived stem cells (HFSCs) as an autologous stem cell (SC) source for ocular surface reconstruction in patients bilaterally affected by LSCD.

Lumican is required for neutrophil extravasation following corneal injury and wound healing.

An important aspect of wound healing is the recruitment of neutrophils to the site of infection or tissue injury. Lumican, an extracellular matrix component belonging to the small leucine rich proteoglycan (SLRP) family, is one of the major keratan sulfate proteoglycans (KSPGs) within the corneal stroma. Increasing evidence indicates that lumican can serve as a regulatory molecule for several cellular processes, including cell proliferation and migration.

Monoallelic expression of Krt12 gene during corneal-type epithelium differentiation of limbal stem cells.

Purpose: The purpose of this study was to characterize a Krt12-Cre knock-in mouse line for corneal epithelium-specific gene ablation and to analyze the allelic selection of the keratin 12 (Krt12) gene during corneal type-epithelium differentiation.

Methods: Knock-in mice were generated by gene targeting. The authors examined the expression patterns of several reporter genes in the corneas of bitransgenic Krt12cre/+/ROSA(EGFP), Krt12Cre/+/ZEG, and Krt12Cre/+/ZAP mouse lines.

Aberrant expression of a beta-catenin gain-of-function mutant induces hyperplastic transformation in the mouse cornea.

Beta-catenin signaling has been shown to play a fundamental role in embryonic development and tumorigenesis. In this study, we investigated the role of beta-catenin (Ctnnb1) in corneal homeostasis and tumorigenesis. Conditional expression of a murine Ctnnb1 gain-of-function mutation alone caused corneal neoplasia and neovascularization, resembling human ocular surface squamous neoplasia (OSSN).

MicroRNAs and regeneration: Let-7 members as potential regulators of dedifferentiation in lens and inner ear hair cell regeneration of the adult newt.

MicroRNAs are known to regulate the expression of many mRNAs by binding to complementary target sequences at the 3'UTRs. Because of such properties, miRNAs may regulate tissue-specific mRNAs as a cell undergoes transdifferentiation during regeneration. We have tested this hypothesis during lens and hair cell regeneration in newts using microarray analysis.

Gene expression signatures in the newt irises during lens regeneration.

Lens regeneration in adult newts is possible by transdifferentiation of the pigment epithelial cells (PECs) of the dorsal iris. The same cells in the ventral iris are not capable of such a process. To understand this difference in regenerative competency, we examined gene expression of 373 genes in the intact dorsal and ventral irises as well as in irises during the process of lens regeneration.

Signaling during lens regeneration.

The newt is one of the few organisms that is able to undergo lens regeneration as an adult. This review will examine the signaling pathways that are involved in this amazing phenomenon. In addition to outlining the current research involved in elucidating the key signaling molecules in lens regeneration, we will also highlight some of the similarities and differences between lens regeneration and development.

The role of Pax-6 in lens regeneration.

Pax-6 is a master regulator of eye development and is expressed in the dorsal and ventral iris during newt lens regeneration. We show that expression of Pax-6 during newt lens regeneration coincides with cell proliferation. By knocking down expression of Pax-6 via treatment with morpholinos, we found that proliferation of iris pigment epithelial cells was dramatically reduced both in vitro and in vivo, and, as a result, lens regeneration was significantly retarded.

Gene expression and discovery during lens regeneration in mouse: regulation of epithelial to mesenchymal transition and lens differentiation.

Purpose: It has been shown that after extracapsular lens removal by anterior capsulotomy in the mouse, the lens can be regenerated. However, as the capsular bag is filled with fibers, epithelial to mesenchymal transition (EMT), an event which is common after cataract surgery as well, takes place during early stages. This study, using a unique mouse model, was undertaken to identify novel regulators and networks in order to more clearly understand secondary cataracts at the molecular level.

BMP inhibition-driven regulation of six-3 underlies induction of newt lens regeneration.

Lens regeneration in adult newts is a classic example of how cells can faithfully regenerate a complete organ through the process of transdifferentiation. After lens removal, the pigment epithelial cells of the dorsal, but not the ventral, iris dedifferentiate and then differentiate to form a new lens. Understanding how this process is regulated might provide clues about why lens regeneration does not occur in higher vertebrates.

Eye on regeneration.

Lens regeneration in newts is a remarkable process, whereby a lost tissue is replaced by transdifferentiation of adult tissues that only a few organisms possess. In this review, we will touch on the approaches being used to study this phenomenon, recent advances in the field of lens regeneration, similarities and differences between development and regeneration, as well as the potential role stem cells may play in understanding this process.

Vertebrate limb regeneration.

In this chapter, we have touched upon some of the key processes of vertebrate limb regeneration from the formation of the wound epithelium to pattern formation, to provide a picture of the many complex and intricate facets of this system. Our synthesis incorporates recent advances in molecular biology, which has revealed some important factors related to the initiation, induction and patterning in limb regeneration.

A novel role of the hedgehog pathway in lens regeneration.

Lens regeneration in the adult newt is a classic example of replacing a lost organ by the process of transdifferentiation. After lens removal, the pigmented epithelial cells of the dorsal iris proliferate and dedifferentiate to form a lens vesicle, which subsequently differentiates to form a new lens. In searching for factors that control this remarkable process, we investigated the expression and role of hedgehog pathway members.

Effects of a CDK inhibitor on lens regeneration.

Lens regeneration in adult newts is always initiated from the dorsal iris by transdifferentiation of the pigment epithelial cells. One of the most important early events should be the ability of pigment epithelial cells to dedifferentiate and re-enter the cell cycle. As a first step in an attempt to study this event, we have decided to examine the effects of a cyclin-dependent kinase-2 inhibitor on lens regeneration.

Lens regeneration in mice: implications in cataracts.

Lens regeneration in adult mice is possible when the lens capsule is left behind after lentectomy. The lens is regenerated by the remaining adherent lens epithelial cells, which differentiate to form lens fibres within days, showing normal morphology and bow regions. Epithelial to mesenchymal cell transformation is also seen during the early stages.

Expression of complement 3 and complement 5 in newt limb and lens regeneration.

Some urodele amphibians possess the capacity to regenerate their body parts, including the limbs and the lens of the eye. The molecular pathway(s) involved in urodele regeneration are largely unknown. We have previously suggested that complement may participate in limb regeneration in axolotls.

Unique expression patterns of the retinoblastoma (Rb) gene in intact and lens regeneration-undergoing newt eyes.

Based on the role of retinoblastoma (Rb) in lens development and in the cell cycle reentry of muscle cells during limb regeneration, we have analyzed expression or Rb patterns in intact and lens regeneration-undergoing newt eyes. We find that in intact newt eye Rb is expressed in the retina as a gradient with higher levels in the photoreceptor layer and virtually no expression in the ganglion layer. In addition, a second gradient was detected within the photoreceptor layer with expression diminishing at the dorsal and ventral regions.

Expression and role of retinoic acid receptor alpha in lens regeneration.

The role of retinoids in eye development has been well studied. Retinoids and their receptors regulate gene expression and morphogenesis of the eye. In this study, a highly specific antagonist of retinoic acid receptor (RAR)-alpha was used in an attempt to study its function in lens regeneration.