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<p>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.</p>

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Felodipine re-positioned as a neuroprotectant via improved optic nerve head blood circulation in retinal ischemic rabbits and ocular hypertensive rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月3日

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  • Takazumi Taniguchi,
  • Takahiro Akaishi,
  • Tatsuya Hata,
  • Rieko Yamashita,
  • Yoshihiko Esaki,
  • Ryo Morofuji,
  • Komei Okabe,
  • Masahiro Fuwa,
  • Yasuko Yamamoto,
  • Li Guo,
  • Soyoung Choi,
  • Vy Luong,
  • Takashi Ota,
  • Najam A. Sharif,
  • M. Francesca Cordeiro,
  • Masaaki Kageyama

摘要

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.