Abstract
Purpose :
Sirtuin 1 (Sirt1) is a histone deacetylase belonging to the sirtuin family which plays a key role in stress response pathways, apoptosis, and inflammation. It has been reported that Sirt1 expresses in normal ocular structures and plays neuroprotective role in various diseases including retinal degeneration. In this study, we intended to investigate the role of intravitreal administration of Sirt1 activator SRT2104 in retinal injury induced by acute ocular hypertention (AOH) and its underlying mechanisms.
Methods :
Intraocular pressure (IOP) was elevated manometrically to 80 mmHg by instilling saline solution into the anterior chamber for 1 h in adult C57BL/6J mice. Intravitreal injection of SRT2104 (200 pmol, 2 μL) was administered immediately after the AOH model was constructed. Immunofluorescence was applied to detect retinal ganglion cells (RGCs) survival and apoptosis, leukocyte infiltration, glial cells activation and inflammation. The protein expression level of related inflammatory factors was observed by western blot. Optical coherence tomography (OCT) and Hematoxylin-eosin (HE) staining were performed to analyse retinal structure. Electroretinogram (ERG) was used to evaluate retinal function.
Results :
The expression of SIRT1 significantly increased after SRT2104 treatment. SRT2104 treatment effectively recovered the inner retinal thickness loss indicated by OCT and HE staining (p < 0.05). Retinal function partly improved on average amplitude and latency of a-wave, b-wave, and oscillatory potentials in ERG analysis (p < 0.05). Furthermore, intravitreal administration of SRT2104 reduced the expression of cleaved-caspase 3, acetyl-p53 and acetyl-NF-κB, declined the levels of inflammatory factors (IL-1β, TNF-α, IL-8, CCL2), and decreased the number of CD45+ leukocyte, activated Iba1+/CD68+ microglia and GFAP+/Vimentin+ astrocytes caused by AOH (all p < 0.05).
Conclusions :
Our data suggested that intravitreal injection of SRT2104 effectively reduced retinal inflammation and protected RGCs from caspase 3 dependent apoptosis via inhibiting deacetylation dependent p53 and NF-κB pathway after AOH injury, and it is expected to be a potential therapeutic method for acute glaucoma.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.