Mesenchymal vs. epithelial extracellular vesicles in corneal epithelial repair, apoptosis, and immunomodulation: An in vitro study.

Corneal injuries often lead to epithelial damage, apoptosis, and inflammation which impact visual function. Effective epithelial healing is critical for optimal vision and functioning of the cornea. Mesenchymal stem/stromal cells (MSCs)-derived extracellular vesicles (EVs) present promising avenues for cell-free therapy, however, evaluation of their specific roles in corneal epithelial injury requires further investigations with due consideration to the endogenous human corneal epithelial cell-derived EVs (HCEC-EVs).

Bone marrow mesenchymal stem cell-derived extracellular vesicles promote corneal epithelial repair and suppress apoptosis via modulation of Caspase-3 in vitro.

Corneal injuries are the major cause of blindness and visual impairment. Available treatments are limited by their efficacy and side effects. Mesenchymal stem cell-derived extracellular vesicles are presumed as functional equivalents and potential candidates for cell-free therapy.

Role of Mesenchymal Stem Cell-Derived Conditioned Medium in Modulating the Benzalkonium Chloride-Induced Cytotoxic Effects in Cultured Corneal Epithelial Cells .

Purpose: Benzalkonium chloride (BAK) is a common preservative in ophthalmic formulations that causes cytotoxic damage to the corneal epithelial cells. This study aims to explore the role of mesenchymal stem cell (MSC)-derived conditioned medium in modulating the BAK-induced cytotoxic effects in cultured human corneal epithelial cells (HCECs) as a cell-free therapeutic agent.

Methods: The cultured HCECs derived from a HCE cell line were treated with BAK (0.

Mesenchymal stem cell-based adjunctive therapy for Pseudomonas aeruginosa-induced keratitis: A proof-of-concept in-vitro study.

Purpose: Pseudomonas aeruginosa-induced keratitis is one of the most severe and challenging forms of corneal infection, owing to its associated intense inflammatory reactions leading to corneal necrosis and dense corneal scar with loss of vision. Since mesenchymal stem cells (MSCs) are reported to possess antimicrobial and immunomodulatory properties, they can be tested as an adjuvant treatment along with the antibiotics which are the current standard of care. This study aims to investigate the anti-bacterial and immunomodulatory roles of human bone marrow MSC-derived conditioned medium (MSC-CM) in P.

Sunset Yellow protects against oxidative damage and exhibits chemoprevention in chemically induced skin cancer model.

Skin cancer and other skin-related inflammatory pathologies are rising due to heightened exposure to environmental pollutants and carcinogens. In this context, natural products and repurposed compounds hold promise as novel therapeutic and preventive agents. Strengthening the skin's antioxidant defense mechanisms is pivotal in neutralizing reactive oxygen species (ROS) and mitigating oxidative stress.

Non-immune and immune functions of interleukin-36γ suppress epithelial repair at the ocular surface.

Regulation of innate inflammation is critical for maintaining tissue homeostasis and barrier function, especially in those interfacing the external environments such as the skin and cornea. Expression of pro-inflammatory cytokines by injured tissues has been shown to exacerbate the inflammatory cascade, causing tissue damage. Interleukin 36, a subfamily of the IL-1 superfamily, consists of three pro-inflammatory agonists-IL36α, IL36β, and IL36γ and an IL36 receptor antagonist (IL36Ra).

Autoregulation of Pax6 in neuronal cells is mediated by Pax6(5a), Pax6(ΔPD), SPARC, and p53.

Background: Pax6, a multifunctional protein and a transcriptional regulator is critical for optimal functioning of neuronal cells. It is known that alternatively spliced Pax6 isoforms and co-expressed interacting proteins mediate cell/tissue specific autoregulation of Pax6, however, underlying mechanism(s) are poorly understood.

Methods And Results: We used Neuro-2a cells to explore the mechanism of autoregulation of Pax6 in neuronal cells whereas NIH/3T3 cells were used as control.

Human Umbilical Cord-Derived Mesenchymal Stem Cells Promote Corneal Epithelial Repair In Vitro.

Corneal injuries are among the leading causes of blindness and vision impairment. Trauma, infectious keratitis, thermal and chemical (acids and alkali burn) injuries may lead to irreversible corneal scarring, neovascularization, conjunctivalization, and limbal stem cell deficiency. Bilateral blindness constitutes 12% of total global blindness and corneal transplantation remains a stand-alone treatment modality for the majority of end-stage corneal diseases.

Allergic conjunctivitis in children: current understanding and future perspectives.

Purpose Of Review: The rising global burden of allergic diseases, particularly in the pediatric population, is of serious concern. Ocular allergy is one of the most common ocular pathologies met in clinical practice. A large proportion of children and adolescents suffer from allergic eye diseases (AEDs), which affect their quality of life.

Limbal Epithelial and Mesenchymal Stem Cell Therapy for Corneal Regeneration.

Corneal pathologies are a major cause of blindness and visual impairment, especially in the developing world. However, not only is there a global shortage of donor corneal tissue, but a significant proportion of these blinding pathologies also carry an unfavourable long-term prognosis for conventional corneal transplantation. In the last few decades, there has been a spurt of research on developing alternate approaches to address corneal blindness, including stem cell therapy.

Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor.

Mesenchymal stromal cells (MSCs) are multipotent stem cells that participate in tissue repair and possess considerable immunomodulatory potential. MSCs have been shown to promote allograft survival, yet the mechanisms behind this phenomenon have not been fully defined. Here, we investigate the capacity of MSCs to suppress the allogeneic immune response by secreting the pleiotropic molecule hepatocyte growth factor (HGF).

Level of hydrogen peroxide affects expression and sub-cellular localization of Pax6.

The Pax6 is a multifunctional pairedbox and homeobox containing transcription factor which is involved in several functions of brain, eyes, and pancreas. It regulates expression of genes involved in cell proliferation, differentiation, inflammation, oxidative stress management, and neuropathy. Dynamic changes in the sub-cellular localization of Pax6 are proposed to regulate its activity, however, the underlying mechanism remains poorly understood.

Optimizing the role of limbal explant size and source in determining the outcomes of limbal transplantation: An in vitro study.

Purpose: Simple limbal epithelial transplantation (SLET) and cultivated limbal epithelial transplantation (CLET) are proven clinical techniques for treating limbal stem cell deficiency (LSCD). However, the ideal size and number of the limbal explants required for transplantation has not been clearly elucidated. This in vitro study aimed to determine the optimal limbal explant size required for complete corneal epithelialization by characterizing the cell expansion.

Level of PAX5 in differential diagnosis of non-Hodgkin's lymphoma.

Background & Objectives: The PAX5, a paired box transcription factor and B-cell activator protein (BSAP), activates B-cell commitment genes and represses non-B-cell lineage genes. About 14 transcript variants of PAX5 have been observed in human. Any alteration in its expression pattern leads to lymphogenesis or associated diseases and carcinogenesis in non-lymphoid tissues.

Cell proliferation and apoptosis in optic nerve and brain integration centers of adult trout Oncorhynchus mykiss after optic nerve injury.

Fishes have remarkable ability to effectively rebuild the structure of nerve cells and nerve fibers after central nervous system injury. However, the underlying mechanism is poorly understood. In order to address this issue, we investigated the proliferation and apoptosis of cells in contralateral and ipsilateral optic nerves, after stab wound injury to the eye of an adult trout Oncorhynchus mykiss.

Pax6 influences expression patterns of genes involved in neuro- degeneration.

Background: Pax6, a highly conserved multifunctional transcription factor, has been critical for neurogenesis and neuronal plasticity. It is presumed that if level of Pax6 approaches either low or null, critical genes responsible for maintaining functional status of neurons or glia would be modulated.

Purpose: Therefore, it has been intended to explore possibility of either direct or indirect influence of Pax6 in neurodegeneration.

Science and Art of Cell-Based Ocular Surface Regeneration.

The potential cause of blindness worldwide includes diseases of the cornea, ocular surface (limbal stem cell deficiency, allergic conjunctivitis, dry eye diseases), and retinal diseases. The presence of stem cells (limbal stem cells) in the basal region of the limbus makes it an important tool for the ocular regeneration and also in maintaining the transparency of eye by replacing the corneal epithelium continuously. Various surgical modalities have been developed like cultured limbal epithelial transplantation, cultured oral mucosal epithelial transplantation, simple limbal epithelial transplantation, etc.

Synthesis, structural investigation, DNA and protein binding study of some 3d-metal complexes with N'-(phenyl-pyridin-2-yl-methylene)-thiophene-2-carboxylic acid hydrazide.

The ligand, N'-(phenyl-pyridin-2-yl-methylene)-thiophene-2-carboxylic acid hydrazide (Hpmtc) derived from thiophene-2-carboxylic acid hydrazide and 2-benzoyl pyridine, and its metal complexes with Co(II), Ni(II), Cu(II) and Zn(II) have been synthesized. These compounds are characterized by elemental analyses, magnetic susceptibility measurements, IR, NMR and UV-Vis spectral studies. The molecular structures of Hpmtc and its Co(II) (1), Ni(II) (2), Cu(II) (3) and Zn(II) (4) complexes are finally determined by X-ray crystallography.

A zinc(II) directed triple-stranded helicate incorporating a nine membered metallamacrocycle: supramolecular cylinders mimicking P1 nuclease.

We report herein the first small molecule based self-assembled fluorescent trinuclear Zn(II) supramolecular cylindrical motif as a structural and functional model of the active site of P1 nuclease. The DNA binding of the same was investigated through UV-Vis, fluorescence and circular dichroism studies.

Predictions on impact of missense mutations on structure function relationship of PAX6 and its alternatively spliced isoform PAX6(5a).

The PAX6 contains two DNA-binding domains, paired domain (PD), homeodomain (HD), and a transactivation domain (TD). Only the crystal structure of PD and the solution structure of HD of PAX6 are known. Mutations in PAX6 show variable penetrance, and expressivity of ocular and neural diseases, but the mechanism is poorly understood.

Functional analysis of missense mutations G36A and G51A in PAX6, and PAX6(5a) causing ocular anomalies.

The PAX6 has been described a "master regulator of eye development". A specific ratio of PAX6, and its alternatively spliced isoform, PAX6(5a), has also been observed essential for optimal function. Mutations into PAX6 lead to a number of ocular, and neuronal defects of variable penetrance and expressivity but the mechanism is either poorly understood or underrepresented.