Protective Efficacy of a Dietary Supplement Based on Forskolin, Homotaurine, Spearmint Extract, and Group B Vitamins in a Mouse Model of Optic Nerve Injury.

Filippo Locri,Maurizio Cammalleri,Dario Rusciano,Massimo Dal Monte,Paola Bagnoli

doi:10.3390/nu11122931

Abstract

Glaucoma is a multifactorial blinding disease with a major inflammatory component ultimately leading to apoptotic retinal ganglion cell (RGC) death. Pharmacological treatments lowering intraocular pressure can help slow or prevent vision loss although the damage caused by glaucoma cannot be reversed. Recently, nutritional approaches have been evaluated for their efficacy in preventing degenerative events in the retina although mechanisms underlying their effectiveness remain to be elucidated. Here, we evaluated the efficacy of a diet supplement consisting of forskolin, homotaurine, spearmint extract, and vitamins of the B group in counteracting retinal dysfunction in a mouse model of optic nerve crush (ONC) used as an in vivo model of glaucoma. After demonstrating that ONC did not affect retinal vasculature by fluorescein angiography, we determined the effect of the diet supplement on the photopic negative response (PhNR) whose amplitude is strictly related to RGC integrity and is therefore drastically reduced in concomitance with RGC death. We found that the diet supplementation prevents the reduction of PhNR amplitude (p < 0.001) and concomitantly counteracts RGC death, as in supplemented mice, RGC number assessed immunohistochemically is significantly higher than that in non-supplemented animals (p < 0.01). Major determinants of the protective efficacy of the compound are due to a reduction of ONC-associated cytokine secretion leading to decreased levels of apoptotic markers that in supplemented mice are significantly lower than in non-supplemented animals (p < 0.001), ultimately causing RGC survival and ameliorated visual dysfunction. Overall, our data suggest that the above association of compounds plays a neuroprotective role in this mouse model of glaucoma thus offering a new perspective in inflammation-associated neurodegenerative diseases of the inner retina.

Highlights

Glaucoma, an optic neuropathy that involves optic nerve (ON) head injury associated with visual field defects, is a leading cause of blindness worldwide [1]
The typical feature of glaucoma is retinal ganglion cell (RGC) degeneration following RGC axon damage that is mainly induced by intraocular pressure (IOP) elevation, RGC death may occur despite normal IOP [1]
To confirm the successful establishment of the optic nerve crush (ONC) model, crushed mice were perfused with fluorescein isothiocyanate-dextran 1 h after ONC and compared with controls to explore the possibility that intra-retinal vasculature would be impaired

Summary

Introduction

An optic neuropathy that involves optic nerve (ON) head injury associated with visual field defects, is a leading cause of blindness worldwide [1]. Pharmacological treatments focused on lowering IOP are currently used to counteract glaucoma progression [3]. The typical feature of glaucoma is retinal ganglion cell (RGC) degeneration following RGC axon damage that is mainly induced by IOP elevation, RGC death may occur despite normal IOP [1]. In this respect, neuroprotective strategies independent from the use of IOP lowering drugs or as an adjuvant of these agents, remain a challenge

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Conclusion