Ali r djalilian

To compare the effects of two decellularization protocols on the characteristics of fabricated COrnea Matrix (COMatrix) hydrogels. Porcine corneas were decellularized with Detergent (De) or Freeze-Thaw (FT)-based protocols. DNA remnant, tissue composition and α-Gal epitope content were measured. The effect of α-galactosidase on α-Gal epitope residue was assessed. Thermoresponsive and light-curable (LC) hydrogels were fabricated from decellularized corneas and characterized with turbidimetric, light-transmission and rheological experiments...

PURPOSE: Cellular senescence is a state of permanent growth arrest whereby a cell reaches its replicative limit. However, senescence can also be triggered prematurely in certain stressors including radiation, oxidative stress, and chemotherapy. This stress-induced senescence has been studied in the context of promoting inflammation, tumor development, and several chronic degenerative diseases of aging. Emerging research has elucidated the role of senescence in various ocular diseases...

Dry eye disease (DED) is a broad term that includes a diverse group of clinical disorders. Aqueous-deficient dry eye (ADDE), a subtype of DED, is characterized by decreased tear production by the lacrimal gland. It can be seen in up to one-third of individuals with DED and can be comorbid with a systemic autoimmune process or occur secondary to an environmental insult. Since ADDE can be a source of long-term suffering and severe visual impairment, early identification and adequate treatment are imperative. Multiple etiologies can underlie ADDE, and it is critical to identify the underlying cause to not only improve the ocular health but also to improve the overall quality of life and well-being of affected individuals...

Superior limbic keratoconjunctivitis (SLK) is an under-recognized condition characterized by a final common pathologic presentation of superior conjunctival and limbal inflammation and staining. Existing literature attributes both microtrauma and local inflammation, frequently in the setting of tear film insufficiency, as the underlying mechanisms that lead to a self-perpetuating pathologic process dependent in on inflammatory cells and signaling. Effective treatments act by targeting inflammation and by mitigating mechanical stressors...

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a definitive therapy for a variety of disorders. One of the complications is acute graft-versus-host disease (aGVHD), which has a high mortality rate. Patients can also develop chronic graft-versus-host disease (cGVHD), a more indolent yet afflicting condition that affects up to 70% of patients. Ocular involvement (oGVHD) is one of the most prevalent presentations of cGVHD and can manifest as dry eye disease, meibomian gland dysfunction, keratitis, and conjunctivitis...

PURPOSE: Mustard gas (MG) is a potent blistering and alkylating agent that has been used for military and terrorism purposes. Ocular surface injuries are common after exposure to MG. This review provides an update on the pathophysiology, ocular surface complications, and treatment options for MG-related ocular injuries. METHODS: Required information was obtained by reviewing various databases such as Cochrane Library, Google Scholar, and PubMed until March 2022...

INTRODUCTION: Mesenchymal stem cells (MSCs) are novel, promising agents for treating ocular surface disorders. MSCs can be isolated from several tissues and delivered by local or systemic routes. They produce several trophic factors and cytokines, which affect immunomodulatory, transdifferentiating, angiogenic, and pro-survival pathways in their local microenvironment via paracrine secretion. Moreover, they exert their therapeutic effect through a contact-dependent manner. AREAS COVERED: In this review, we discuss the characteristics, sources, delivery methods, and applications of MSCs in ocular surface disorders...

The corneal epithelium is composed of nonkeratinized stratified squamous cells and has a significant turnover rate. Limbal integrity is vital to maintain the clarity and avascularity of the cornea as well as regeneration of the corneal epithelium. Limbal epithelial stem cells (LESCs) are located in the basal epithelial layer of the limbus and preserve this homeostasis. Proper functioning of LESCs is dependent on a specific microenvironment, known as the limbal stem cell niche (LSCN). This structure is made up of various cells, an extracellular matrix (ECM), and signaling molecules...

The limbal stem cells niche (LSCN) is an optimal microenvironment that provides the limbal epithelial stem cells (LESCs) and strictly regulates their proliferation and differentiation. Disturbing the LSCN homeostasis can lead to limbal stem cell dysfunction (LSCD) and subsequent ocular surface aberrations, such as corneal stromal inflammation, persistent epithelial defects, corneal neovascularisation, lymphangiogenesis, corneal opacification, and conjunctivalization. As ocular surface disorders are considered the second main cause of blindness, it becomes crucial to explore different therapeutic strategies for restoring the functions of the LSCN...

PURPOSE: The purpose of this study was to assess the effect of a second povidone-iodine (PVP-I) application at the time of donor tissue recovery on overall tissue quality and to analyze the rate of positive fungal and bacterial rim cultures before and after implementing increased PVP-I exposure. METHODS: The left cornea was recovered after a single application of PVP-I, while the right cornea was recovered after double PVP-I application in research-consented donors...

Ocular surface exposure to nitrogen mustard (NM) leads to severe ocular toxicity which includes the separation of epithelial and stromal layers, loss of endothelial cells, cell death, and severe loss of tissue function. No definitive treatment for mustard gas-induced ocular surface disorders is currently available. The research was conducted to investigate the therapeutic potential of mesenchymal stem cell-conditioned media (MSC-CM) in NM-induced corneal wounds. NM was added to different types of corneal cells, the ocular surface of porcine, and the ocular surface of mice, followed by MSC-CM treatment...

A 54-year-old man with noncontributory medical history presented to an ophthalmologist in January 2022 after 10 days of irritation in his right eye. The patient recounts having felt something get into his eye and under his contact lens (CL) while he was climbing into his car, but he was unsure what the foreign body may have been. Initial examination by the clinician found uncorrected distance visual acuity of 20/100-2 with a corneal abrasion, 4+ corneal edema, and 3+ conjunctival injection, for which he was placed on topical antibiotics (ocuflox and tobradex) with a bandage CL...

PURPOSE: Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) have been demonstrated to possess great potential in preclinical models. An efficient biomanufacturing platform is necessary for scale up production for clinical therapeutic applications. The aim of this study is to investigate the potential differences in neuro-regenerative properties of MSC-derived EVs generated in 2D versus 3D culture systems. METHOD: Human bone marrow MSCs (BM-MSCs) were cultured in 2D monolayer and 3D bioreactor systems...

Peripheral ulcerative keratitis (PUK) is a rare but serious ocular condition that is an important clinical entity due to its ophthalmological and systemic implications. It is characterized by progressive peripheral corneal stromal thinning with an associated epithelial defect and can be associated with an underlying local or systemic pro-inflammatory condition, or present in an idiopathic form (Mooren ulcer). Associated conditions include autoimmune diseases, systemic and ocular infections, dermatologic diseases, and ocular surgery...

Corneal injuries are a major cause of blindness worldwide. To restore corneal integrity and clarity, there is a need for regenerative bio-integrating materials for in-situ repair and replacement of corneal tissue. Here, we introduce Light-curable COrnea Matrix (LC-COMatrix), a tunable material derived from decellularized porcine cornea extracellular matrix containing un-denatured collagen and sulfated glycosaminoglycans. It is a functionalized hydrogel with proper swelling behavior, biodegradation, and viscosity that can be cross-linked in situ with visible light, providing significantly enhanced biomechanical strength, stability, and adhesiveness...

PURPOSE: To investigate the effects of topical and perilesional interferon alpha-2b as primary treatment for ocular surface squamous neoplasia (OSSN). METHODS: In this prospective interventional case series, topical interferon alpha-2b (3 MIU/mL) was used as the initial treatment of OSSN, with perilesional interferon alpha-2b (3 MIU/mL) added based on clinical response. The primary outcome was complete tumor resolution. Spearman's rank correlation test was used to investigate the association of complete tumor resolution and time to resolution with baseline tumor characteristics and the American Joint Committee on Cancer (AJCC) classification for OSSN...

The protective function and transparency provided by the corneal epithelium are dependent on and maintained by the regenerative capacity of limbal epithelial stem cells (LESCs). These LESCs are supported by the limbal niche, a specialized microenvironment consisting of cellular and non-cellular components. Disruption of the limbal niche, primarily from injuries or inflammatory processes, can negatively impact the regenerative ability of LESCs. Limbal stem cell deficiency (LSCD) directly hampers the regenerative ability of the corneal epithelium and allows the conjunctival epithelium to invade the cornea, which results in severe visual impairment...

Purpose: Mesenchymal stromal cells (MSCs) have been shown to enhance tissue repair as a cell-based therapy. In preparation for a phase I clinical study, we evaluated the safety, dosing, and efficacy of bone marrow-derived MSCs after subconjunctival injection in preclinical animal models of mice, rats, and rabbits. Methods: Human bone marrow-derived MSCs were expanded to passage 4 and cryopreserved. Viability of MSCs after thawing and injection through small-gauge needles was evaluated by vital dye staining...

Conflicting results have been reported regarding the effects of 1,25 OH-vitamin D3 on corneal wound healing. Therefore, we undertook this study to determine whether the observed differences are dose related. The dose-dependent effects of 1,25 OH-vitamin D3 on corneal wound healing were evaluated using scratch assays on human corneal limbal-epithelial cells (HCLEs) and in vivo mouse corneal epithelial debridement. To evaluate the anti-inflammatory effects of 1,25 OH-vitamin D3 , macrophages were stimulated by a Toll-Like Receptor (TLR) ligand followed by treatment with the 10-6  M, 10-7  M and 10-8  M 1,25 OH-vitamin D3 ...

PURPOSE: Bioactive substrates can be used therapeutically to enhance wound healing. Here, we evaluated the effect of an in-situ thermoresponsive hydrogel from decellularized porcine cornea ECM, COMatrix (COrnea Matrix), for application as an ocular surface bandage for corneal epithelial defects. METHODS: COMatrix hydrogel was fabricated from decellularized porcine corneas. The effects of COMatrix hydrogel on attachment and proliferation of human corneal epithelial cells (HCECs) were evaluated in vitro...