UVB induced reactivation leads to HSV1 in the corneas of virtually all latently infected mice and requires STING to develop corneal disease.

Reactivation of latent herpes simplex type 1 results in virus returning to the cornea leading to recurrent herpetic stromal keratitis (rHSK). We compare two competing models to reactivate viruses from latency, UV-B irradiation and cyclophosphamide (CP). Results revealed that while both result in corneal recrudescence, only UV-B irradiation results in rHSK. To better understand the dynamics of reactivation, we analyzed corneas for both the presence of infectious viruses and the dynamics of exposure to multiple reactivations using UV-B. We noted that multiple reactivations result in progressively worse corneal disease. We also noted that expression of IFNα and STING, surragate markers for the presence of virus, are induced by the presence of reactivated virus. Studies to determine the importance of STING to the development of HSK revealed that in the absence of STING, mice do not develop significant HSK and the magnitude of the infiltrate of CD45+ cells in these corneas is significantly reduced. The resulting paucity of CD45+CD11b+GR-1+F4/80-neutrophils, and to a lesser extent CD45+CD11b+GR-1-F4/80+ macrophages in B6-STING KO mice following reactivation is likely the underlying cause for lack of rHSK as has been noted by ourselves and others. These results underscore the critical importance of STING's role in developing rHSK.

UV-B induced HSV-1 reactivation leads to infectious virus in the corneas of virtually all latently infected mice and requires an intact STING to develop herpetic stromal keratitis.

Reactivation of latent herpes simplex type 1 results in virus returning to the cornea leading to recurrent herpetic stromal keratitis (rHSK). We compare two competing models to reactivate viruses from latency, UV-B irradiation and cyclophosphamide. Results revealed that while both result in corneal recrudescence, only UV-B irradiation results in rHSK. To better understand the dynamics of reactivation, we analyzed corneas for both the presence of infectious viruses and the dynamics of exposure to multiple reactivations using UV-B. We noted that multiple reactivations result in progressively worse corneal disease. We also noted that expression of IFNα and STING, surragate markers for the presence of virus, are induced by the presence of reactivated virus. Studies to determine the importance of STING to the development of HSK revealed that in the absence of STING, mice do not develop significant HSK and the magnitude of the infiltrate of CD45 + cells in these corneas is significantly reduced. The resulting paucity of CD45 + CD11b + GR-1 + F4/80-neutrophils, and to a lesser extent CD45 + CD11b + GR-1-F4/80 + macrophages in B6-STING KO mice following reactivation is likely the underlying cause for lack of rHSK as has been noted by ourselves and others. These results underscore the critical importance of STING's role in developing rHSK.

Role of NK T cells in transplantation with particular emphasis on corneal transplantation.

Natural killer T cells (NKT cells) are a unique subset of the immune system that possess characteristics of both an innate and adaptive immune response. This study reviews the reported roles of NKT cells in different solid transplantations such as cardiac, skin, liver, and corneal grafts as well as investigates a novel role of NKT cells in steroid-resistant corneal rejections. It is unknown why there is late corneal graft rejection despite being treated with immunosuppression. Our experimental data suggests NKT cells are playing a crucial part in steroid-resistant late graft rejections. While the pathophysiology of acute rejection is better understood, the process of chronic graft rejection is much less clear. Our data suggests NKT cells as a potential therapeutic target to prevent chronic transplant rejection which needs further investigation.

Acanthamoeba Keratitis, Pathology, Diagnosis and Treatment.

Acanthamoeba keratitis is an unusual corneal infection that is recently increasing in frequency and is often contracted by contact lens wearers, someone who experienced recent eye trauma, or someone exposed to contaminated waters. Acanthamoeba survive in air, soil, dust, and water. Therefore, eye trauma and poor contact lens hygiene practices lead to the entrapment of debris and thus infection. Acanthamoeba keratitis results in severe eye pain, inflammation, and defects of the epithelium and stroma that can potentially result in vision loss if not diagnosed early and treated promptly. The disease can be diagnosed using corneal scrape/biopsy, polymerase chain reactions, impression cytology, or in vivo confocal microscopy. Once diagnosed, it is usually treated with an antimicrobial combination therapy of biguanide and aromatic diadine eye drops for several months. Advanced stages of the disease result in vision loss and the need for corneal transplants. Avoiding the risk factors and diagnosing the disease early are the most effective ways to combat Acanthamoeba keratitis.