Deakin University
Browse

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

Download (1.53 MB)
journal contribution
posted on 2024-08-20, 03:23 authored by Viswanthram Palanivel, Vivek Gupta, Nitin Chitranshi, Ole Tietz, Roshana Vander Wall, Reuben Blades, Kanishka Pushpitha Maha Thananthirige, Akanksha Salkar, Chao Shen, Mehdi Mirzaei, Veer GuptaVeer Gupta, Stuart L Graham, Devaraj Basavarajappa
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.

History

Journal

PNAS Nexus

Volume

3

Article number

pgae299

Pagination

1-15

Location

Oxford, Eng.

Open access

  • Yes

ISSN

2752-6542

eISSN

2752-6542

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Editor/Contributor(s)

Abramov A

Issue

8

Publisher

Oxford University Press

Usage metrics

    Research Publications

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC