Preliminary study of low-dose photodynamic therapy on the oxidative stress response of Cutibacterium acnes.

PURPOSE: The objective of this study was to investigate the influence of photodynamic therapy (PDT) employing different, lower 5-aminolevulinic acid (ALA) dosages on the proliferative activity of Cutibacterium acnes (C. acnes). METHODS: In this in vitro bacterial experiment, we examined the effects of PDT using different doses of ALA (0.05 mmol/L; 0.1 mmol/L; 0.5 mmol/L; 1.0 mmol/L; 2.5 mmol/L). To elucidate the underlying mechanisms, we assessed colony-forming units (CFUs), bacterial staining for live/dead, antioxidant enzyme activity, and gene expression of oxidative stress markers following treatment with different doses of ALA-PDT. RESULTS: Our findings demonstrate that CFU, bacterial staining for live/dead, as well as the activity and gene expression of superoxide dismutase (SOD) and catalase (CAT), all exhibited significant increases when the ALA concentration was 0.1/0.5 mmol/L. However, both CFU and cell growth of C. acnes decreased when the ALA concentration reached 1.0 mmol/L. CONCLUSION: Lower concentration of ALA-PDT (0.1/0.5 mmol/L) appears to promote the growth of C.acnes while higher doses (1.0 /2.5 mmol/L) are associated with eradication. The procedure is possibly mediated by the activation of antioxidant-related genes and enzyme expression in cells.

Inhibition of mTOR signaling by rapamycin protects photoreceptors from degeneration in rd1 mice.

Retinitis pigmentosa (RP) is an inherited retinal degenerative disease that begins with defective rod photoreceptor function, followed by impaired cone function, and complete blindness in its late stage. To date, however, there is no effective treatment for RP. By carrying a nonsense mutation in the Pde6b gene, rd1 mice display elevated cGMP in conjunction with higher intracellular Ca 2+ in their rod photoreceptors, resulting in fast retinal degeneration. Ca 2+ has been linked to activation of the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway integrates extracellular and intracellular signals to sense the supply of nutrients and plays a central role in regulating protein and lipid synthesis as well as apoptosis and autophagy. In the present study, we showed that mTOR and phosphorylated mTOR (p-mTOR, activated form of mTOR) are up-regulated in rd1 photoreceptors at postnatal day 10 (P10), a pre-degenerative stage. Moreover, the downstream effectors of mTOR, such as pS6K and S6K, are also increased, suggesting activation of the mTOR signaling pathway. Intravitreal administration of rapamycin, a negative regulator of mTOR, inhibits the mTOR pathway in rd1 photoreceptors. Consequently, the progression of retinal degeneration is slower and retinal function is enhanced, possibly mediated by activation of autophagy in the photoreceptors. Taken together, these results highlight rapamycin as a potential therapeutic avenue for retinal degeneration.