| First Author | Tao L | Year | 2022 |
| Journal | Exp Eye Res | Volume | 214 |
| Pages | 108877 | PubMed ID | 34863682 |
| Mgi Jnum | J:319666 | Mgi Id | MGI:6865423 |
| Doi | 10.1016/j.exer.2021.108877 | Citation | Tao L, et al. (2022) Repressing c-Jun N-terminal kinase signaling mitigates retinal pigment epithelium degeneration in mice with failure to clear all-trans-retinal. Exp Eye Res 214:108877 |
| abstractText | Retinal pigment epithelium (RPE) cell apoptosis arising from all-trans-retinal (atRAL) is in close contact with the etiology of dry age-related macular degeneration (AMD) and autosomal recessive Stargardt's disease (STGD1), but its underlying mechanisms remain elusive. In this study, we reported that c-Jun N-terminal kinase (JNK) activation facilitated atRAL-induced apoptosis of RPE cells. Reactive oxygen species production and endoplasmic reticulum stress were identified as two of major upstream events responsible for activating JNK signaling in atRAL-loaded RPE cells. Inhibiting JNK signaling rescued RPE cells from apoptosis induced by atRAL through attenuating caspase-3 activation leading to poly-ADP-ribose polymerase (PARP) cleavage, and DNA damage response. Abca4(-/-)Rdh8(-/-) mice upon light exposure exhibit rapidly increased accumulation of atRAL in the retina, and display severe RPE degeneration, a primary attribute of dry AMD and STGD1. Reducing JNK signaling by intraperitoneally injected JNK-IN-8 was highly effective in preventing RPE atrophy and apoptosis in light-exposed Abca4(-/-)Rdh8(-/-) mice. These findings afford a further understanding for contribution of JNK activation by atRAL to retinal damage. |
