Neuropeptide Y receptor activation preserves inner retinal integrity through PI3K/Akt signaling in a glaucoma mouse model

Title
Neuropeptide Y receptor activation preserves inner retinal integrity through PI3K/Akt signaling in a glaucoma mouse model
Publication Date
2024-08
Author(s)
Palanivel, Viswanthram
Gupta, Vivek
Chitranshi, Nitin
( author )
OrcID: https://orcid.org/0000-0002-6508-9865
Email: nchitran@une.edu.au
UNE Id une-id:nchitran
Tietz, Ole
Vander Wall, Roshana
Blades, Reuben
Thananthirige, Kanishka Pushpitha Maha
Salkar, Akanksha
Shen, Chao
Mirzaei, Mehdi
Gupta, Veer
Graham, Stuart L
Basavarajappa, Devaraj
Type of document
Journal Article
Language
en
Entity Type
Publication
Publisher
Oxford University Press
Place of publication
United Kingdom
DOI
10.1093/pnasnexus/pgae299
UNE publication id
une:1959.11/71659
Abstract

Neuropeptide Y (NPY), an endogenous peptide composed of 36 amino acids, has been investigated as a potential therapeutic agent for neurodegenerative diseases due to its neuroprotective attributes. This study investigated the neuroprotective effects of NPY in a mouse model of glaucoma characterized by elevated intraocular pressure (IOP) and progressive retinal ganglion cell degeneration. Elevated IOP in mice was induced through intracameral microbead injections, accompanied by intravitreal administration of NPY peptide. The results demonstrated that NPY treatment preserved both the structural and functional integrity of the inner retina and mitigated axonal damage and degenerative changes in the optic nerve under high IOP conditions. Further, NPY treatment effectively reduced inflammatory glial cell activation, as evidenced by decreased expression of glial fibrillary acidic protein and Iba-1. Notably, endogenous NPY expression and its receptors (NPY-Y1R and NPY-Y4R) levels were negatively affected in the retina under elevated IOP conditions. NPY treatment restored these changes to a significant extent. Molecular analysis revealed that NPY mediates its protective effects through the mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling pathways. These findings highlight the therapeutic potential of NPY in glaucoma treatment, underscoring its capacity to preserve retinal health, modulate receptor expression under stress, reduce neuroinflammation, and impart protection against axonal impairment.

Link
Citation
PNAS Nexus, 3(8), p. 1-15
ISSN
2752-6542
Start page
1
End page
15
Rights
Attribution 4.0 International

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