The cornea is directly exposed to cigarette smoke, and smoking is a risk factor for several corneal diseases including dry eye syndrome. Currently, heated tobacco products (HTPs) are widely used as substitutes for cigarette smoking around the world. In the present study, we investigated the molecular mechanism(s) leading to cellular injury induced by cigarette smoke extract (CSE) or HTPs. Exposure to CSE perturbed the formation of tight junctions, leading to an increase in cell volume, a decrease in transepithelial electrical resistance (TER) in the human corneal epithelial cell-transformed (HCE-T) cell line. Moreover, CSE exposure induced both lipid peroxidation and ferrous [Fe(II)] ion accumulation in autolysosomal compartments. Interestingly, a cleaved form of ferritin appeared when HCE-T cells were incubated with CSE. This aberrant ferritin processing was suppressed by treatment with autophagy inhibitors. Furthermore, the CSE-induced cell death was suppressed by either ferrostatin-1 or deferoxamine (DFO). CSE exposure also promoted the expression of cytokines whereas DFO treatment inhibited the CSE-induced expression of these cytokines. Exposure to HTPs also induced both HCE-T cell death and cleaved ferritin accumulation in a concentration- and time-dependent manner. These results indicated that CSE or HTPs activated the ferroptosis signaling pathway, which contributed to corneal epithelial cell injury.

No abstract

The corneal epithelium is continuously exposed to oxygen, light, and environmental substances. Excessive exposure to those stresses is thought to be a risk factor for eye diseases. Photokeratitis is damage to the corneal epithelium resulting in a painful eye condition caused by unprotected exposure to UV rays, usually from sunlight, and is often found in people who spend a long time outdoors. In modern life, human eyes are exposed to artificial light from light-emitting diode (LED) displays of computers and smartphones, and it has been shown that short-wavelength (blue) LED light can damage eyes, especially photoreceptors. However, the effect of blue LED light on the cornea is less understood. In addition, it is important to develop new treatments for preserving human eyesight and eye health from light stress. Here, we used human corneal epithelial cells-transformed (HCE-T) cells as an in-vitro model to investigate the protective effect of NSP-116, an imidazolyl aniline derivative, against the oxidative stress induced by light in the corneal epithelium. Treatment with 10 µM NSP-116 significantly increased the cell viability and reduced the death ratio following UV or blue LED light exposure. Furthermore, NSP-116 treatment decreased light-induced reactive oxygen species production and preserved the mitochondrial membrane potential. Immunoblotting data showed that NSP-116 suppressed the stress response pathway. Finally, NSP-116 treatment prevented corneal epithelial apoptosis induced by blue LED light in an in-vivo mouse model. In conclusion, NSP-116 has a protective effect against oxidative stress and corneal cell death from both UV and blue LED light exposure.

No abstract

Spinal muscular atrophy (SMA) is a progressive neuromuscular disease, associated with motoneuron loss and muscle wasting. Numerous SMA-causative mutations have been reported in survival motor neuron (SMN) gene(s); however, the pathogenic mechanism underlying SMA remains unclear. In the present study, we showed that SMN modulates the expression of transcription factor EB (TFEB), a master regulator of lysosomal genes that plays a key role in lysosome function, autophagy, and the mammalian target of rapamycin (mTOR) signaling pathway. The transfection of small interfering RNA (siRNA) targeting SMN caused a reduction in TFEB expression in the motoneuron-like NSC-34 cell line. In differentiated NSC-34 cells, either SMN or TFEB knockdown resulted in reduced lysosomes at neurites and the atypical accumulation of swollen and enlarged lysosomes in cell bodies. SMN knockdown caused the reduced expression of lysosome-related genes, resulting in the decline of lysosomal degradation and increased autophagic flux. These SMN-depletion-induced aberrations in lysosomes and autophagy could be rescued by the exogenous expression of TFEB. Furthermore, SMN depletion in NSC-34 cells resulted in the decreased phosphorylation of mTOR and its downstream signals. Finally, SMA transgenic mice exhibited reduced TFEB and lysosomal protein expression and the inactivation of mTOR signaling in the lumbar spinal cord at postnatal day 11, compared with their counterparts. These findings indicated that SMN regulates lysosomal gene expression and functions by altering TFEB expression in motoneurons. The targeting of lysosomes might represent a new strategy for the treatment of SMA.