Cargando…

PnPP-19 Peptide as a Novel Drug Candidate for Topical Glaucoma Therapy Through Nitric Oxide Release

PURPOSE: Evaluation of PnPP-19 safety and efficacy in reducing the intraocular pressure (IOP) of animals with healthy (normotensive) and ocular hypertensive eyes. PnPP-19 is a synthetic peptide designed from Phoneutria nigriventer spider toxin PnTx2-6. METHODS: Toxicity tests used chicken chorioalla...

Descripción completa

Detalles Bibliográficos
Autores principales: da Silva, Carolina Nunes, Dourado, Lays Fernanda Nunes, de Lima, Maria Elena, da Silva Cunha-Jr, Armando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422904/
https://www.ncbi.nlm.nih.gov/pubmed/32855879
http://dx.doi.org/10.1167/tvst.9.8.33
_version_ 1783570088467628032
author da Silva, Carolina Nunes
Dourado, Lays Fernanda Nunes
de Lima, Maria Elena
da Silva Cunha-Jr, Armando
author_facet da Silva, Carolina Nunes
Dourado, Lays Fernanda Nunes
de Lima, Maria Elena
da Silva Cunha-Jr, Armando
author_sort da Silva, Carolina Nunes
collection PubMed
description PURPOSE: Evaluation of PnPP-19 safety and efficacy in reducing the intraocular pressure (IOP) of animals with healthy (normotensive) and ocular hypertensive eyes. PnPP-19 is a synthetic peptide designed from Phoneutria nigriventer spider toxin PnTx2-6. METHODS: Toxicity tests used chicken chorioallantoic membranes. Electroretinograms (ERGs) were recorded before and after administration of different doses of PnPP-19 on the eyes of Wistar rats. Histological sections of corneas and retinas were prepared. The efficacy of PnPP-19 in reducing IOP was evaluated for normotensive and ocular hypertensive animals using a tonometer. Ocular hypertension was induced in the right eye through injection of hyaluronic acid (HA) into the anterior chamber. ERG was recorded before and after glaucoma induction. The eyes were enucleated, and the corneas and retinas were histologically evaluated. RESULTS: PnPP-19 showed no toxicity, being safe for ocular application. A single topical instillation of one eye drop of the peptide solution was able to reduce IOP, both in healthy and ocular hypertensive rats, for 24 hours, without eliciting any apparent toxicity. PnPP-19 is a nitric oxide inducer and the results suggest that it may improve the conventional outflow of aqueous humor (AH), preventing the progression of optic nerve degeneration. CONCLUSIONS: PnPP-19 has great potential to emerge as a promising drug for the treatment of ocular hypertension. TRANSLATIONAL RELEVANCE: We regard our findings as exciting progress in translational glaucoma research, combining drug discovery, natural product research, and pharmacology, which may contribute to the establishment of new therapies for the treatment of this disease.
format Online
Article
Text
id pubmed-7422904
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher The Association for Research in Vision and Ophthalmology
record_format MEDLINE/PubMed
spelling pubmed-74229042020-08-26 PnPP-19 Peptide as a Novel Drug Candidate for Topical Glaucoma Therapy Through Nitric Oxide Release da Silva, Carolina Nunes Dourado, Lays Fernanda Nunes de Lima, Maria Elena da Silva Cunha-Jr, Armando Transl Vis Sci Technol Article PURPOSE: Evaluation of PnPP-19 safety and efficacy in reducing the intraocular pressure (IOP) of animals with healthy (normotensive) and ocular hypertensive eyes. PnPP-19 is a synthetic peptide designed from Phoneutria nigriventer spider toxin PnTx2-6. METHODS: Toxicity tests used chicken chorioallantoic membranes. Electroretinograms (ERGs) were recorded before and after administration of different doses of PnPP-19 on the eyes of Wistar rats. Histological sections of corneas and retinas were prepared. The efficacy of PnPP-19 in reducing IOP was evaluated for normotensive and ocular hypertensive animals using a tonometer. Ocular hypertension was induced in the right eye through injection of hyaluronic acid (HA) into the anterior chamber. ERG was recorded before and after glaucoma induction. The eyes were enucleated, and the corneas and retinas were histologically evaluated. RESULTS: PnPP-19 showed no toxicity, being safe for ocular application. A single topical instillation of one eye drop of the peptide solution was able to reduce IOP, both in healthy and ocular hypertensive rats, for 24 hours, without eliciting any apparent toxicity. PnPP-19 is a nitric oxide inducer and the results suggest that it may improve the conventional outflow of aqueous humor (AH), preventing the progression of optic nerve degeneration. CONCLUSIONS: PnPP-19 has great potential to emerge as a promising drug for the treatment of ocular hypertension. TRANSLATIONAL RELEVANCE: We regard our findings as exciting progress in translational glaucoma research, combining drug discovery, natural product research, and pharmacology, which may contribute to the establishment of new therapies for the treatment of this disease. The Association for Research in Vision and Ophthalmology 2020-07-22 /pmc/articles/PMC7422904/ /pubmed/32855879 http://dx.doi.org/10.1167/tvst.9.8.33 Text en Copyright 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Article
da Silva, Carolina Nunes
Dourado, Lays Fernanda Nunes
de Lima, Maria Elena
da Silva Cunha-Jr, Armando
PnPP-19 Peptide as a Novel Drug Candidate for Topical Glaucoma Therapy Through Nitric Oxide Release
title PnPP-19 Peptide as a Novel Drug Candidate for Topical Glaucoma Therapy Through Nitric Oxide Release
title_full PnPP-19 Peptide as a Novel Drug Candidate for Topical Glaucoma Therapy Through Nitric Oxide Release
title_fullStr PnPP-19 Peptide as a Novel Drug Candidate for Topical Glaucoma Therapy Through Nitric Oxide Release
title_full_unstemmed PnPP-19 Peptide as a Novel Drug Candidate for Topical Glaucoma Therapy Through Nitric Oxide Release
title_short PnPP-19 Peptide as a Novel Drug Candidate for Topical Glaucoma Therapy Through Nitric Oxide Release
title_sort pnpp-19 peptide as a novel drug candidate for topical glaucoma therapy through nitric oxide release
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422904/
https://www.ncbi.nlm.nih.gov/pubmed/32855879
http://dx.doi.org/10.1167/tvst.9.8.33
work_keys_str_mv AT dasilvacarolinanunes pnpp19peptideasanoveldrugcandidatefortopicalglaucomatherapythroughnitricoxiderelease
AT douradolaysfernandanunes pnpp19peptideasanoveldrugcandidatefortopicalglaucomatherapythroughnitricoxiderelease
AT delimamariaelena pnpp19peptideasanoveldrugcandidatefortopicalglaucomatherapythroughnitricoxiderelease
AT dasilvacunhajrarmando pnpp19peptideasanoveldrugcandidatefortopicalglaucomatherapythroughnitricoxiderelease