PURPOSE: Oxidative stress plays a critical role in the pathogenesis of glaucoma. Glutathione is a major antioxidant molecule present in intracellular or extracellular space. Herein, we aimed to examine circulating glutathione level in normal tension glaucoma (NTG), which comprises the largest proportion of glaucoma disease in the Korean population. METHODS: Nineteen NTG patients (NTG group) and 30 age- and gender-matched normal control subjects (control group) were included. Antecubital venous puncture was performed between 8 and 10 o'clock in the morning to obtain a 4 mL venous blood sample. Total glutathione level was measured by the spectrophotometric method at 412 nm. Correlation of total glutathione level with mean deviation and pattern standard deviation from the Humphrey visual field test was analyzed in the NTG group. RESULTS: Total glutathione level in circulating blood was 524.02 +/- 231.09 nmol and 586.06 +/- 156.08 nmol in the NTG group and the control group, respectively. The difference between these values was not statistically significant (p = 0.121, F = 2.212). Age had no significant effect on circulating total glutathione level in either the NTG group (p = 0.171, r = -0.328) or the control group (p = 0.380, r = -0.166). In the NTG group, circulating total glutathione level had no significant relationship with mean deviation (p = 0.226, F = 1.636) and pattern standard deviation (p = 0.200, F = 1.766) after correcting for age and gender. CONCLUSIONS: In NTG patients, circulating total glutathione levels were not different compared to those of normal subjects.
Disease Progression ; Eye/*metabolism ; Female ; Glutathione/*metabolism ; Humans ; Intraocular Pressure ; Low Tension Glaucoma/*metabolism/*pathology ; Male ; Middle Aged ; Oxidative Stress/*physiology ; Tonometry, Ocular

Tropomyosin receptor kinase A (TrkA) protein is a receptor tyrosine kinase encoded by the NTRK1 gene. TrkA signaling mediates the proliferation, differentiation, and survival of neurons and other cells following stimulation by its ligand, the nerve growth factor.Chromosomal rearrangements of the NTRK1 gene result in the generation of TrkA fusion protein, which is known to cause deregulation of TrkA signaling. Targeting TrkA activity represents a promising strategy for the treatment of cancers that harbor the TrkA fusion protein. In this study, we evaluated the TrkA-inhibitory activity of the benzoxazole compound KRC-108. KRC-108 inhibited TrkA activity in an in vitro kinase assay, and suppressed the growth of KM12C colon cancer cells harboring an NTRK1 gene fusion.KRC-108 treatment induced cell cycle arrest, apoptotic cell death, and autophagy. KRC-108 suppressed the phosphorylation of downstream signaling molecules of TrkA, including Akt, phospholipase Cγ, and ERK1/2. Furthermore, KRC-108 exhibited antitumor activity in vivo in a KM12C cell xenograft model. These results indicate that KRC-108 may be a promising therapeutic agent for Trk fusion-positive cancers.