Engineered Knockout of TRPA1 Inhibits Laser-Induced Choroidal Neovascularization Along With Associated TGFß1 Expression and Neutrophil Infiltration.

We examined the effects of gene ablation and chemical inhibition of transient receptor potential ankyrin 1 (TRPA1) on the growth of experimental argon laser-induced choroidal neovascularization (CNV) in mice. CNV was induced in the eyes of 6- to 8-week-old TRPA1-null (knockout [KO]) and wild-type (WT) mice by argon laser irradiation. Gene expression analysis was performed in laser-injured tissues at days 1 and 3. CNV growth was evaluated at day 14. Reciprocal bone marrow transplantation was performed between each genotype to identify the components responsible for either recipient tissue or bone marrow-derived inflammatory cells. Our results show that laser irradiation successfully induced CNV growth at the site of laser injury. The size of induced CNV was significantly smaller in KO mice than in WT mice at day 14, as determined by angiography with fluorescein isothiocyanate-dextran. Invasion of neutrophils, but not macrophages, was suppressed in association with suppression of the expression of transforming growth factor ß1 and interleukin 6 in laser-irradiated KO tissue. Bone marrow transplantation indicated that the genotype of the recipient mouse, but not of inflammatory cells, is attributable to the KO phenotype. Systemic administration of a TRPA1 antagonist also reduced the CNV in a WT mouse. In conclusion, TRPA1 signaling in local cells is involved in growth of laser-induced CNV. The phenotype was not attributable to vascular endothelial cells and inflammatory cells. Blocking TRPA1 signal may therefore be a potential treatment strategy for CNV-related ocular diseases.

Late-onset acute disseminated encephalomyelitis followed by optic neuritis without anti-myelin oligodendrocyte glycoprotein antibodies: a biopsied case report.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) followed by optic neuritis (ADEM-ON) is characterized by the following features: early onset, monophasic or multiphasic ADEM followed by one or more episodes of ON, and the presence of serum anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. CASE REPORT: We report a case of ADEM-ON without anti-MOG antibodies in a 78-year-old woman. The patient developed acute-onset neurological findings and was diagnosed with ADEM. She was treated with intravenous methylprednisolone (IVMP), and oral corticosteroids. Her clinical symptoms and MRI findings subsequently improved. Left optic neuritis emerged 6 months later, and we made a diagnosis of ADEM-ON. A brain biopsy performed during the acute phase of ADEM showed perivascular infiltration of macrophages with demyelination. CONCLUSION: The majority of the reported ADEM-ON cases are pediatric cases with serum anti-MOG antibodies, but our patient was the elderly, without anti-MOG antibodies. Moreover, the pathological features of our case were similar to those observed in patients with typical ADEM and in patients with anti-MOG antibody-positive ADEM. Although ADEM-ON is related to the presence of anti-MOG antibodies, factors other than anti-MOG antibodies could contribute to the development of ADEM-ON.

Deterioration after Liver Transplantation and Transthyretin Stabilizer Administration in a Patient with ATTRv Amyloidosis with a Leu58Arg (p.Leu78Arg) TTR Variant.

We herein report a 44-year-old Japanese man with hereditary transthyretin amyloidosis (ATTRv amyloidosis) harboring the variant Leu58Arg (p.Leu78Arg) in TTR in whom we conducted an observational study with liver transplantation (LT) and transthyretin (TTR) stabilizers (tafamidis and diflunisal) for 9 years. This patient showed gradual deterioration of sensory, motor, and autonomic neuropathy symptoms after LT. Furthermore, cardiac amyloidosis gradually developed. Although the present case showed deterioration of the symptoms after disease-modifying treatments, LT might be suitable in patients with the same variant if they are young and in good condition due to a long survival after LT.

A unique case of primary effusion lymphoma-like lymphoma showing disappearance and recurrence of the body cavity effusion.

Primary effusion lymphoma-like lymphoma (PEL-LL) is a rare B-cell lymphoma that the etiology remains unclear. We describe a case of PEL-LL with a pleuropericardial effusion. Diagnosis required long period of time as it followed a unique progress of disappearance and recurrence of the body cavity effusion. We finally had a diagnosis of B-cell lymphoma by the immunocytochemistry of effusion using the cell block procedure. Authors consider that it is valuable to actively try the cell block procedure at the time of the first drainage for early diagnosis, if the body cavity effusion due to the malignancy is suspected.