Felodipine re-positioned as a neuroprotectant via improved optic nerve head blood circulation in retinal ischemic rabbits and ocular hypertensive rats
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The vasodilatory and neuroprotective properties of felodipine were characterized in normal and ischemic rabbit eyes, an ocular hypertension (OHT) rat model, and cultured human neuron-like cells. Blood flow in the optic nerve head (ONH) was measured using laser speckle flowgraphy following intravitreally injected felodipine into normal and ischemic rabbit eyes receiving endothelin-1 injection. Felodipine concentrations in the retina-choroidal tissue were determined using mass spectrometry, and ocular safety was assessed using in-life examinations and histopathology in rabbits. The number of retinal ganglion cells (RGCs) was counted following intravitreal felodipine injection in hypertonic saline-induced OHT rats. The in vitro neuroprotective effects of felodipine against vincristine-induced nuclear loss and neurite shortening were evaluated in differentiated SH-SY5Y neuron-like cells. Felodipine increased ONH blood flow in a dose-dependent manner in normal rabbit eyes. High felodipine dosage (780 nmol/eye) improved blood circulation in endothelin-1-induced ischemic eyes. The ONH blood flow response to felodipine correlated with tissue concentration-time profiles. Even high dose of felodipine did not cause any ocular toxicity. Furthermore, felodipine protected SH-SY5Y cells against vincristine-induced damage and prevented OHT-induced RGC cell loss following its administration (40 nmol/eye). Felodipine can act as a neuroprotectant against glaucomatous neuropathy via improved ONH microcirculation and direct neuroprotection of RGCs.
Date Issued
2025-07-03
Date Acceptance
2025-06-30
Citation
Scientific Reports, 2025, 15
ISSN
2045-2322
Publisher
Nature Portfolio
Journal / Book Title
Scientific Reports
Volume
15
Copyright Statement
© The Author(s) 2025 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40610740
PII: 10.1038/s41598-025-09733-1
Subjects
BLOCKER
Calcium channel blocker
Felodipine
Glaucoma
GLAUCOMA
Multidisciplinary Sciences
Neuroprotection
Ocular blood flow
PRESSURE
Retinal ganglion cells
Science & Technology
Science & Technology - Other Topics
Publication Status
Published
Coverage Spatial
England
Article Number
23811
Date Publish Online
2025-07-03