Abstract
Purpose :
Pituitary adenylate cyclase activating polypeptide (PACAP) has been shown to exert potent neuroprotective effects in central nervous system and retina disorders. However, whether PACAP could attenuate retinal neurodegeneration induced by acute ocular hypertension (AOH) and the precise mechanisms remain unknown. In this study, we aim to investigate the effects of PACAP on retinal ganglion cells (RGCs) survival, apoptosis, retinal reactive gliosis and vascular inflammation in mouse model of AOH injury.
Methods :
PACAP was injected into the vitreous body immediately after inducing the AOH injury. Hematoxylin & eosin staining and optical coherence tomography were used to evaluate the loss of retina tissue. Electroretinogram was used to evaluate the visual function of retina. TUNEL assay was used to detect the apoptotic cells. Immunofluorescence and western blot were employed to evaluate the protein expression level.
Results :
PACAP treatment significantly attenuated the losses of retina thickness and RGCs, and improved the b-wave amplitudes of scotopic electroretinogram after AOH injury. Additionally, PACAP treatment remarkably reduced the number of apoptotic cells in AOH injury, and inhibited the upregulation of Bax, cleaved caspase3 and downregulation of Bcl-xL induced by AOH injury. Moreover, PACAP markedly abrogated retinal reactive gliosis and vascular inflammation, as demonstrated by the downregulation of GFAP, Iba-1, CD68 and CD45 in PACAP-treated mice. Furthermore, upregulated expression of NF-κB and phosphorylated NF-κB induced by AOH injury were attenuated by PACAP treatment.
Conclusions :
These results demonstrated that PACAP could attenuate retinal injury by inhibiting the Bax-Caspase3 dependent apoptotic pathway and NF-κB dependent inflammatory pathway.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.