Abstract
Purpose :
Melatonin, a hormone mainly secreted by pineal gland, is believed to be involved in exerting the protective effects in the aged-related and neurodegenerative diseases through silent information regulator type 1 (SIRT1)-dependent pathway. However，the effect of melatonin on retinal ganglion cells (RGCs) senescence was unknown. Thus, in this study, we aimed to examine the effect of melatonin on RGCs senescence following optic nerve crush (ONC) and explore whether SIRT1 was involved in this process.
Methods :
ONC model was established in this study. EX527, an inhibitor of SIRT1, was injected intraperitoneally into mice 30 minutes before ONC and melatonin was administrated abdominally into mice after ONC every day. The immunofluorescence and western blot were used to evaluate the expression of SIRT1, p16 and p53. β-gal staining was employed to detected senescence cells. Hematoxylin & eosin (HE) staining, retina flat-mounts and optical coherence tomography (OCT) were used to evaluate the loss of retina tissue. Pattern electroretinogram (p-ERG) was performed to evaluate the visual function of retina.
Results :
Melatonin stimulated the expression of SIRT1 in RGCs 3 days after ONC, which was normally expressed in RGCs of normal C57BL/6J mice and decreased after ONC. Meanwhile, the melatonin therapy restored the decreased RGCs numbers and ganglion cell complex (GCC) thickness (p<0.001, 0.01, respectively) 14 days after ONC. Moreover, the treatment of melatonin suppressed the ONC-induced senescence index at day 3 by decreasing the expression of p16, p53 and β-gal positive cells (p<0.05). Furthermore, the p-ERG showed that melatonin improved the amplitude of P50 and N95 (p<0.05). Besides, administration of EX527 decreased the protective effect of melatonin after ONC, which revealed that SIRT1 was involved in the process of melatonin regulating RGCs senescence after ONC.
Conclusions :
Our data suggested that melatonin ameliorated the RGCs senescence via the SIRT1-dependent pathway following ONC, which may provide an important insight for the treatment of RGC senescence.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.