MERTK Inhibitor Associated Retinal Toxicity in a Human.

Purpose: The MER proto-oncogene tyrosine kinase (MERTK) helps maintain the homeostasis of the retinal pigmented epithelium (RPE). Additionally, MERTK regulates the innate immune system. As such inhibition of MERTK has gained recent interest as a target for cancer therapeutics.

Insights into spaceflight-associated neuro-ocular syndrome with review of intraocular and orbital findings.

Purpose Of Review: Spaceflight-associated neuro-ocular syndrome (SANS) remains a phenomenological term, and advances in ophthalmic imaging as well as new insights from ground-based experiments have given support to new theories of how SANS develops and what may be done to counter it.

Recent Findings: SANS has been postulated to arise from elevated intracranial pressure (ICP) during long-duration spaceflight (LDSF). However, recent work has shown that acute microgravity exposure does not increase ICP, and the effect of cephalad fluid shifts on ICP in microgravity remain unknown.

Outcomes of chronic macula-off retinal detachment repair.

Purpose: There have been disparate outcomes in the few studies that have looked at anatomic success and visual acuity (VA) in chronic retinal rhegmatogenous detachment (RRD) repair. Chronic retinal detachments (RD) without a posterior vitreous detachment (PVD) occur in young myopes often secondary to an atrophic hole. These patients are often asymptomatic, and studies report good surgical anatomic results.

Delayed Epithelial Healing with Corneal Edema and Haze After Photorefractive Keratectomy Using Intraoperative Mitomycin C.

We report an unusual presentation of presumed mitomycin C toxicity with possible subsequent hypersensitization to other medication toxicities. A 50-year-old female presented three months after photorefractive keratectomy with intraoperative mitomycin C for the management of persistent epithelial defects, corneal haze, and edema. She was found to have used an expansive and rapidly changing medical regimen which may have caused additional toxicity.

Delayed Perforation of an Intrastromal Corneal Ring Segment into the Anterior Chamber: A Case Report and Review of the Literature.

Intrastromal corneal ring segments (ICRSs) are an effective treatment for stabilizing and normalizing corneal shape in patients with keratoconus and other corneal ectasias. Intraoperative segment perforation through the corneal endothelium into the anterior chamber (AC) is an uncommon but known complication. However, perforation into the AC postoperatively is an exceedingly rare complication with only 3 reported cases in the literature.

Corneal Refractive Surgery in Patients with a History of Herpes Simplex Keratitis: A Narrative Review.

The incidence of herpes simplex keratitis (HSK) in patients following corneal refractive surgery is higher than in the general population, and several case reports of ocular morbidity in HSK infection following corneal refractive surgery have been published. HSK is listed by the American Academy of Ophthalmology as a relative contraindication to corneal refractive surgery, although specifics have not been further elucidated. This review summarizes the current literature regarding reactivation of HSK following corneal refractive surgery and provides a guideline for considering corneal refractive surgery in a patient with a previous history of HSK.

Pancreatic Tumor Microenvironment Modulation by EphB4-ephrinB2 Inhibition and Radiation Combination.

Purpose: A driving factor in pancreatic ductal adenocarcinoma (PDAC) treatment resistance is the tumor microenvironment, which is highly immunosuppressive. One potent immunologic adjuvant is radiotherapy. Radiation, however, has also been shown to induce immunosuppressive factors, which can contribute to tumor progression and formation of fibrotic tumor stroma.

Inhibition of EphB4-Ephrin-B2 Signaling Reprograms the Tumor Immune Microenvironment in Head and Neck Cancers.

Identifying targets present in the tumor microenvironment that contribute to immune evasion has become an important area of research. In this study, we identified EphB4-ephrin-B2 signaling as a regulator of both innate and adaptive components of the immune system. EphB4 belongs to receptor tyrosine kinase family that interacts with ephrin-B2 ligand at sites of cell-cell contact, resulting in bidirectional signaling.

Inhibition of EphB4-Ephrin-B2 Signaling Enhances Response to Cetuximab-Radiation Therapy in Head and Neck Cancers.

The clinical success of targeted therapies such as cetuximab and radiotherapy (RT) is hampered by the low response rates and development of therapeutic resistance. In the current study, we investigated the involvement of EphB4-ephrin-B2 protumorigenic signaling in mediating resistance to EGFR inhibition and RT in head and neck cancers. We used patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma (HNSCC) and HNSCC cell lines to test our hypothesis.

Hypofractionated Radiotherapy Is Superior to Conventional Fractionation in an Orthotopic Model of Anaplastic Thyroid Cancer.

Background: Anaplastic thyroid cancer (ATC) is an aggressive and highly lethal disease with poor outcomes and resistance to therapy. Despite multimodality treatment, including radiation therapy and chemotherapy, response rates remain <15%, with a median time to progression of less than three months. Recent advances in radiotherapy (RT) delivery and gene-expression profiling may help guide patient selection for personalized therapy.

Transgenic up-regulation of Claudin-6 decreases fine diesel particulate matter (DPM)-induced pulmonary inflammation.

Claudin-6 (Cldn6) is a tetraspanin transmembrane protein that contributes to tight junctional complexes and has been implicated in the maintenance of lung epithelial barriers. In the present study, we tested the hypothesis that genetic up-regulation of Cldn-6 influences inflammation in mice exposed to short-term environmental diesel particulate matter (DPM). Mice were subjected to ten exposures of nebulized DPM (PM2.

Cigarette smoke and decreased oxygen tension inhibit pulmonary claudin-6 expression.

Purpose: Chronic obstructive pulmonary disease is a condition involving perturbed barrier integrity coincident with both emphysema and inflammation of the airways, and smoking is considered a major risk factor. Claudins (Cldns) stabilize barriers and contribute to tight junctions by preventing paracellular transport of extracellular fluid constituents.

Methods: To determine Cldn6 was differentially influenced by tobacco smoke, Cldn6 was evaluated in cells and tissues by q-PCR, immunoblotting, and immunohistochemistry following exposure.

Up-Regulation of Claudin-6 in the Distal Lung Impacts Secondhand Smoke-Induced Inflammation.

It has long been understood that increased epithelial permeability contributes to inflammation observed in many respiratory diseases. Recently, evidence has revealed that environmental exposure to noxious material such as cigarette smoke reduces tight junction barrier integrity, thus enhancing inflammatory conditions. Claudin-6 (Cldn6) is a tetraspanin transmembrane protein found within the tight junctional complex and is implicated in maintaining lung epithelial barriers.