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Abstract #128569 Published in IGR 25-3

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

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.

Ophthalmology Innovation Center, Santen Pharmaceutical Co., Ltd, 8916-16 Takayama-cho, Ikoma-shi, 630 - 0101, Nara, Japan. takazumi.taniguchi@santen.com.

Classification:

15 Miscellaneous

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