A truncated form of neuropeptide Y (NPY 3-36) provided neuroprotection in experimental glaucoma without causing the retinal vasoconstriction seen with full-length NPY.
Y2/Y5 selectiveTruncated NPY (3-36) achieved neuroprotection through selective receptor activation without Y1-mediated vasoconstriction
What the researchers found
Truncated NPY (3-36) selectively activated neuroprotective pathways (via Y2/Y5 receptors) while avoiding vasoconstriction (mediated by Y1 receptors), demonstrating that receptor-selective peptide analogs can dissociate beneficial from harmful effects in glaucoma treatment.
Why it matters
Glaucoma is a leading cause of blindness, and neuroprotection of retinal ganglion cells is a major unmet need. This study shows that peptide modification can eliminate dangerous side effects while preserving therapeutic benefit, advancing NPY-based therapies toward clinical viability.
The numbers in context
- NPY(1-36): caused transient vasoconstriction via Y1 receptor
- NPY(3-36): no vasoconstriction; selectively activates Y2 and Y5 receptors
- NPY(3-36) preserved retinal ganglion cell density under elevated IOP
- Reduced astrocytic and microglial activation
How the study worked
Animal study in mice using fluorescein angiography to assess retinal vascular responses after intravitreal injection of NPY analogs, followed by evaluation of neuroprotective effects in an experimental glaucoma model.
Who was studied
Mice with elevated intraocular pressure (glaucoma model). Intravitreal injection of NPY(1-36) and NPY(3-36) analogs.
What this study cannot tell us
Animal study only — mouse retinal physiology may differ from human; intravitreal injection is invasive; long-term safety and efficacy of repeated NPY (3-36) dosing not established; glaucoma models may not fully replicate human disease.
How to read the evidence
Preclinical animal study with clear mechanistic demonstration. Strong proof-of-concept but requires translation to larger animal models and human trials.
When this study was published
Published in 2025, reflecting ongoing innovation in peptide-based neuroprotection.
The bigger picture
This elegant receptor-selectivity approach could be applied beyond ophthalmology. Many peptides have both beneficial and harmful effects mediated by different receptors — truncation and modification strategies could unlock safer peptide therapeutics across multiple fields.
Questions still open
- Could NPY (3-36) be delivered through less invasive routes, such as eye drops or sustained-release implants?
- Does the neuroprotective effect persist long-term, or would repeated injections be needed?
- Would this approach work in other neurodegenerative conditions where NPY has shown promise?
Common questions
What is neuropeptide Y?
Why can't the full version of this peptide be used for glaucoma?
Read the original research
Selective Receptor Modulation by Truncated Neuropeptide Y (3-36) Dissociates Vasoconstriction from Neuroprotection in Experimental Glaucoma.
Molecular neurobiology, 63(1), 334
Citation
Palanivel, Viswanthram; Basavarajappa, Devaraj; Salkar, Akanksha; Komáromy, András M; Tietz, Ole; Eva, Taslima Akter; Chitranshi, Nitin; Mirzaei, Mehdi; Gupta, Veer; You, Yuyi; Graham, Stuart L; Gupta, Vivek. (2025). Selective Receptor Modulation by Truncated Neuropeptide Y (3-36) Dissociates Vasoconstriction from Neuroprotection in Experimental Glaucoma.. Molecular neurobiology, 63(1), 334. https://doi.org/10.1007/s12035-025-05636-4