Title:Melatonin Alleviates Pyroptosis of Retinal Neurons Following Acute Intraocular Hypertension
Volume: 20
Issue: 3
Author(s): Yu Zhang, Yanxia Huang , Limin Guo , Yun Zhang , Mingxuan Zhao , Fuyao Xue , Cheng Tan , Jufang Huang and Dan Chen *
Affiliation:
- Department of Human Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013,China
Keywords:
Acute HIOP, NLRP3, retinal neurons, melatonin, NF-κ B, pyroptosis.
Abstract:
Background: Glaucoma is a multifactorial optic neuropathy progressively characterized
by structural loss of Retinal Ganglion Cells (RGCs) and irreversible loss of vision. High Intraocular
Pressure (HIOP) is a high-risk factor for glaucoma. It has been reported that the mechanisms of
the loss of RGCs are explored in-depth after acute HIOP injury, such as apoptosis, autophagy, and
necrosis. However, pyroptosis, a novel type of pro-inflammatory cell programmed necrosis, is rarely
reported after HIOP injury. Research studies also showed that melatonin (MT) possesses substantial
anti-inflammatory properties. However, whether melatonin could alleviate retinal neuronal
death, especially pyroptosis, by HIOP injury is still unclear.
Objective: This study explored pyroptosis of retinal neurons and the effects of melatonin in preventing
retinal neurons from pyroptosis after acute HIOP injury.
Methods: An acute HIOP model of rats was established by increasing the IOP followed by reperfusion.
Western Blot (WB) was adopted to detect molecules related to pyroptosis at the protein level,
such as GSDMD, GASMDp32, Caspase-1, and caspase-1 p20, and the products of inflammatory reactions,
such as IL -18 and IL-1β. At the same time, immunofluorescence (IF) was used to co-localize
caspase-1 with retinal neurons to determine the position of caspase-1 expression. Morphologically,
ethidium homodimer III staining, a method commonly used to evaluate cell death, was carried
out to stain dead cells. Subsequently, Lactate Dehydrogenase (LDH) cytotoxicity assay kit was
used to quantitatively analyze the LDH released after cell disruption.
Results: The results suggested that pyroptosis played a vital role in retinal neuronal death, especially
in the Ganglion Cell Layer, by acute HIOP injury and peaked at 6h after HIOP injury. Furthermore,
it was found that melatonin (MT) might prevent retinal neurons of pyroptosis via NF-κ
B/NLRP3 axis after HIOP injury in rats.
Conclusion: Melatonin treatment might be considered a new strategy for protecting retinal neurons
against pyroptosis following acute HIOP injury.
