Congenital Corneal Endothelial Dystrophies Resulting From Novel De Novo Mutations.

Purpose: To describe 2 cases of congenital corneal endothelial edema resulting from novel de novo mutations.

Methods: Case A patient was a 15-month-old white child and case B patient was a 3-year-old Hispanic child presenting with bilateral cloudy corneas since birth. Clinicopathologic findings are presented.

Autoregulatory CD8 T cells depend on cognate antigen recognition and CD4/CD8 myelin determinants.

Objective: To determine the antigenic determinants and specific molecular requirements for the generation of autoregulatory neuroantigen-specific CD8(+) T cells in models of multiple sclerosis (MS).

Methods: We have previously shown that MOG35-55-specific CD8(+) T cells suppress experimental autoimmune encephalomyelitis (EAE) in the C57BL/6 model. In this study, we utilized multiple models of EAE to assess the ability to generate autoregulatory CD8(+) T cells.

TCF4 Triplet Repeat Expansion and Nuclear RNA Foci in Fuchs' Endothelial Corneal Dystrophy.

Purpose: Expansion of the intronic CTG18.1 triplet repeat locus within TCF4 contributes significant risk to the development of Fuchs' endothelial corneal dystrophy (FECD) in Eurasian populations, but the mechanisms by which the expanded repeats result in degeneration of the endothelium have been hitherto unknown. The purpose of this study was to examine FECD endothelial samples for the presence of RNA nuclear foci, the hallmark of toxic RNA, as well as evidence of haploinsufficiency of TCF4.

Disease exacerbation of multiple sclerosis is characterized by loss of terminally differentiated autoregulatory CD8+ T cells.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). Although its etiology remains unknown, pathogenic T cells are thought to underlie MS immune pathology. We recently showed that MS patients harbor CNS-specific CD8+ Tregs that are deficient during disease relapse.

The disease-ameliorating function of autoregulatory CD8 T cells is mediated by targeting of encephalitogenic CD4 T cells in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS, and CD8 T cells are the predominant T cell population in MS lesions. Given that transfer of CNS-specific CD8 T cells results in an attenuated clinical demyelinating disease in C57BL/6 mice with immunization-induced experimental autoimmune encephalomyelitis (EAE), we investigated the cellular targets and mechanisms of autoreactive regulatory CD8 T cells. In this study we report that myelin oligodendrocyte glycoprotein peptide (MOG35-55)-induced CD8 T cells could also attenuate adoptively transferred, CD4 T cell-mediated EAE.

Modulation of immune function occurs within hours of therapy initiation for multiple sclerosis.

Daily administration of FDA-approved glatiramer acetate (GA) has beneficial effects on clinical course of relapsing remitting multiple sclerosis (RRMS). Although mechanisms of GA-action have been widely investigated and partially understood, immediate immune dynamics following GA-therapy are unknown. In the present study, we characterized the immediate effects of GA on phenotype, quantity and function of immune cells in MS patients.

Pharmaceutical composition for treating macular degeneration (WO2012079419).

A pharmaceutical composition composed of several traditional Chinese medicines is claimed to treat age-related macular degeneration (AMD). This represents a novel and alternative therapeutic solution for wet AMD, with the potential advantage of treating both the symptoms and the underlying causes of this devastating degenerative retinal disease.

Next-generation therapeutic solutions for age-related macular degeneration.

Age-related macular degeneration (AMD) is the primary cause of irreversible blindness among the elderly in the western world. To date, no cure is available and the current anti-VEGF therapy has only shown limited efficacy in improving visual acuity in neovascular AMD. The etiology of AMD remains elusive but research over the past decade has uncovered characteristic features of the disease.

IL-17A-dependent CD4+CD25+ regulatory T cells promote immune privilege of corneal allografts.

IL-17A is a proinflammatory cytokine that has received attention for its role in the pathogenesis of several autoimmune diseases. IL-17A has also been implicated in cardiac and renal allograft rejection. Accordingly, we hypothesized that depletion of IL-17A would enhance corneal allograft survival.

Identification of a novel gene, CIA6, required for normal pyrenoid formation in Chlamydomonas reinhardtii.

Chlamydomonas reinhardtii possesses a CO(2)-concentrating mechanism (CCM) that allows the alga to grow at low CO(2) concentrations. One common feature seen in photosynthetic organisms possessing a CCM is the tight packaging of Rubisco within the cell. In many eukaryotic algae, Rubisco is localized to the pyrenoid, an electron-dense structure within the chloroplast.

Paradigm shifts in the role of CD4+ T cells in keratoplasty.

Corneal transplantation is the oldest, most common, and arguably the most successful form of organ transplantation. In uncomplicated first-time cases, corneal allografts enjoy a success rate of up to 90% even though the transplants are performed without HLA matching or the use of systemic immunosuppressive drugs. In rodents, corneal allografts transplanted across entire MHC and multiple minor histocompatibility barriers enjoy long-term survival in >50% of the hosts, while skin grafts invariably undergo immune rejection.

IL-17 promotes immune privilege of corneal allografts.

Corneal allograft rejection has been described as a Th1-mediated process involving IFN-γ production. However, it has been reported that corneal allograft rejection soars in IFN-γ(-/-) mice or mice treated with anti-IFN-γ mAb. Th17 is a recently described IL-17A-producing Th cell population that has been linked to renal and cardiac graft rejection, which was originally thought to be Th1-mediated.

Two different regulatory T cell populations that promote corneal allograft survival.

Purpose: To compare and contrast the T regulatory cells (Tregs) induced by anterior chamber (AC) injection of antigen with those induced by orthotopic corneal allografts.

Methods: Anterior chamber-associated immune deviation (ACAID) Tregs were induced by injecting C57BL/6 spleen cells into the AC of BALB/c mice. Delayed-type hypersensitivity responses to C57BL/6 alloantigens were evaluated by a conventional ear swelling assay.

Identification and characterization of two closely related beta-carbonic anhydrases from Chlamydomonas reinhardtii.

Aquatic photosynthetic organisms such as the green alga Chlamydomonas reinhardtii respond to low-CO(2) conditions by inducing a CO(2) concentrating mechanism (CCM). Important components of the CCM are the carbonic anhydrases (CAs), zinc metalloenzymes that catalyze the interconversion of CO(2) and HCO(-)(3). Six CAs have previously been identified in C.