Cultivated autologous limbal epithelial cell (CALEC) transplantation for limbal tem cell deficiency: a phase I/II clinical trial of the first xenobiotic-free, serum-free, antibiotic-free manufacturing protocol developed in the US.

We developed a two-stage manufacturing process utilizing cultivated autologous limbal epithelial cells (CALEC), the first xenobiotic-free, serum-free, antibiotic-free protocol developed in the United States, to treat blindness caused by unilateral limbal stem cell deficiency (LSCD) and conducted a single-center, single-arm, phase I/II clinical trial. Primary outcomes were feasibility (meeting release criteria) and safety (ocular infection, corneal perforation, or graft detachment). Participant eligibility included male or female participants age 18 to <90 years old and ability to provide written informed consent with LSCD.

Topical neurokinin-1 receptor antagonism ameliorates ocular pain and prevents corneal nerve degeneration in an animal model of dry eye disease.

Introduction: Ocular pain is a common complaint to eye care providers, associated with a variety of ocular conditions, among which dry eye disease (DED) is affecting millions of people worldwide. Despite being highly prevalent, ocular pain is not managed adequately in the clinic.

Objectives: The aim of this study was to investigate the analgesic potential of neurokinin-1 receptor (NK1R) antagonism in DED.

Immunology in corneal transplantation-From homeostasis to graft rejection.

Immunology depends on maintaining a delicate balance within the human body, and disruptions can result in conditions such as autoimmune diseases, immunodeficiencies, and hypersensitivity reactions. This balance is especially crucial in transplantation immunology, where one of the primary challenges is preventing graft rejection. Such rejection can lead to organ failure, increased patient mortality, and higher healthcare costs due to the limited availability of donor tissues relative to patient needs.

Antagonizing NK-1R modulates pain perception following corneal injury.

Substance P (SP) expressed by corneal nerves, is an 11-amino acid long neuropeptide from the tachykinin family, encoded by the Tac1 gene, and binds to neurokinin receptors. SP overexpression is associated with various pathological responses in the cornea including vasodilation, pain, inflammation, and angiogenesis in the normally avascular tissue. This study investigates the role of neurokinin-1 receptor (NK-1R) mediated signaling in nociception, nerve regeneration, and neuronal activation following mechanical corneal injury in mice.

TNF-α Suppression Attenuates Limbal Stem Cell Damage in Ocular Injury.

Purpose: Ocular chemical injuries often cause uveal inflammation, upregulation of TNF-α at the limbus, and subsequent limbal stem cell (LSC) damage. In this study, we investigate the protective role of TNF-α suppression in LSC survival.

Methods: Corneal alkali injuries were performed using NaOH as previously described by our group.

Activation of α2B/2C adrenergic receptor ameliorates ocular surface inflammation through enhancing regulatory T cell function.

There is an unmet need for effectively treating dry eye disease (DED), a T cell-mediated chronic, inflammatory ocular surface disorder. Given the potential of nonneuronal adrenergic system in modulating T cell response, we herein investigated the therapeutic efficacy and the underlying mechanisms of a specific alpha 2 adrenergic receptor agonist (AGN-762, selective for α2B/2C receptor subtypes) in a mouse model of DED. Experimental DED was treated with the AGN-762 by oral gavage, either at disease induction or after disease establishment, and showed sustained amelioration, along with reduced expression of DED-pathogenic cytokines in ocular surface tissues, decreased corneal MHC-IICD11b cells and lymphoid Th17 cells, and higher function of regulatory T cells (Treg).

Hepatocyte growth factor upregulates MMP1 and MMP10 expression and resolves corneal fibrosis.

Different therapeutic modalities, including steroids, have been used to treat corneal scarring. However, the ability of steroids to reduce corneal scarring is limited and associated with numerous side effects. Our previous studies have demonstrated that topical hepatocyte growth factor (HGF) after corneal injury suppresses the development of stromal scars.

A limbal stem cell deficiency murine model with residual limbal stem cells.

Bilateral limbal stem cell deficiency (LSCD) is a significant cause of corneal blindness and is more difficult to treat, as compared with unilateral LSCD because no source of autologous limbal stem cells (LSCs) remains in these patients. Thus, bilateral patients could be candidates for treatment with allogeneic LSC transplants that require long-term systemic immunosuppression therapy. Thus, if possible, for the correct candidates, using autologous LSCs could be a preferred treatment.

Primary Conjunctival Molluscum Contagiosum in a Patient With Ocular Graft-Versus-Host Disease.

Purpose: Primary conjunctival molluscum contagiosum (MC) is rare and usually reported in patients with acquired immunodeficiency syndrome. In this study, we present a case of bilateral primary conjunctival MC in a patient with ocular graft-versus-host disease (oGVHD).

Methods: This is a case report study.

Assessment of Corneal Graft Outcomes in a Murine Model of Endothelial Keratoplasty.

: In this study, we establish a protocol for evaluating the outcomes of endothelial keratoplasty, including graft survival, rejection, or failure. Additionally, we also evaluate the alloimmune response in graft recipients. : We performed EK using C57BL/6 (allogeneic) and BALB/c (syngeneic) as donors and BALB/c mice as recipients.

Neuropeptide alpha-Melanocyte stimulating hormone preserves corneal endothelial morphology in a murine model of Fuchs dystrophy.

Fuchs endothelial corneal dystrophy is a heterogenous disease with multifactorial etiology, and genetic, epigenetic, and exogenous factors contributing to its pathogenesis. DNA damage plays a significant role, with ultraviolet-A (UV-A) emerging as a key contributing factor. We investigate the potential application of neuropeptide α-melanocyte stimulating hormone (α-MSH) in mitigating oxidative stress induced endothelial damage.

Complications After Pediatric Penetrating Keratoplasty: An IRIS Registry Study.

Purpose: To describe the frequency of postoperative complications in children undergoing penetrating keratoplasty (PK).

Methods: This retrospective cohort study included pediatric patients (aged 0-18 years) in the Intelligent Research in Sight (IRIS) Registry who underwent primary PK between January 2013 and December 2020. Patients were identified using Current Procedure Terminology codes.

Substance P regulates memory Th17 cell generation and maintenance in chronic dry eye disease.

Substance P is a neuropeptide expressed by nerves and an array of cells that serves as a critical mediator of neuroinflammation. Our recent work has demonstrated that blocking the preferred receptor for substance P, neurokinin 1 receptor, effectively suppresses the induction of acute dry eye disease by preserving regulatory T-cell function, while inhibiting antigen-presenting cell maturation and subsequent generation of effector Th17 cells. Clinically, dry eye disease is a chronic disorder characterized by sustained ocular surface inflammation, which is mediated by long-lived memory Th17 cells demonstrated in our well-established chronic dry eye disease model.

Neurokinin-1 Receptor Antagonism Reduces Nonallergic Ocular Redness in a Rabbit Model.

To evaluate the therapeutic efficacy of topical application of a neurokinin-1 receptor (NK1R) antagonist in a rabbit model of nonallergic ocular redness. Nonallergic ocular redness was induced in rabbits by a single, topical application of dapiparzole hydrochloride eye drops (0.5%, 1%, 2%, or 5%).

Immunopathological mechanisms and clinical manifestations of ocular graft-versus-host disease following hematopoietic stem cell transplantation.

Graft-versus-host disease is among the most common clinical complications following allogeneic hematopoietic stem cell transplantation. It causes inflammation-mediated destruction and dysfunction of various organ systems including ocular tissues in 60-90% of the patients and is termed ocular GVHD (oGVHD). In oGVHD, donor-derived T-cells recognize host antigens as foreign, resulting in immune dysregulation, inflammation and fibrosis of lacrimal glands, meibomian glands, cornea, and conjunctiva.

Contact lenses as novel tear fluid sampling vehicles for total RNA isolation, precipitation, and amplification.

The tear fluid is a readily accessible, potential source for biomarkers of disease and could be used to monitor the ocular response to contact lens (CL) wear or ophthalmic pathologies treated by therapeutic CLs. However, the tear fluid remains largely unexplored as a biomarker source for RNA-based molecular analyses. Using a rabbit model, this study sought to determine whether RNA could be collected from commercial CLs and whether the duration of CL wear would impact RNA recovery.

Suppression of Neovascularization by Topical and Subconjunctival Bevacizumab After High-Risk Corneal Transplantation.

Purpose: To assess the effectiveness of topical and subconjunctival bevacizumab in suppressing vascularization in graft and host bed after high-risk corneal transplantation.

Design: Secondary analysis of prospective, randomized, double-blind, placebo-controlled multicentric clinical trial.

Participants: The study includes patients aged > 18 years who underwent high-risk penetrating keratoplasty, which was defined as corneal vascularization in ≥ 1 quadrants of the corneal graft and host bed, excluding the limbus.