A Dietary Combination of Forskolin with Homotaurine, Spearmint and B Vitamins Protects Injured Retinal Ganglion Cells in a Rodent Model of Hypertensive Glaucoma

Maurizio Cammalleri,Paola Bagnoli,Massimo Dal Monte,Dario Rusciano,Rosario Amato

doi:10.3390/nu12041189

Abstract

There is indication that nutritional supplements protect retinal cells from degeneration. In a previous study, we demonstrated that dietary supplementation with an association of forskolin, homotaurine, spearmint extract and B vitamins efficiently counteracts retinal dysfunction associated with retinal ganglion cell (RGC) death caused by optic nerve crush. We extended our investigation on the efficacy of dietary supplementation with the use of a mouse model in which RGC degeneration depends as closely as possible on intraocular pressure (IOP) elevation. In this model, injecting the anterior chamber of the eye with methylcellulose (MCE) causes IOP elevation leading to RGC dysfunction. The MCE model was characterized in terms of IOP elevation, retinal dysfunction as determined by electrophysiological recordings, RGC loss as determined by brain-specific homeobox/POU domain protein 3A immunoreactivity and dysregulated levels of inflammatory and apoptotic markers. Except for IOP elevation, dysfunctional retinal parameters were all recovered by dietary supplementation indicating the involvement of non-IOP-related neuroprotective mechanisms of action. Our hypothesis is that the diet supplement may be used to counteract the inflammatory processes triggered by glial cell activation, thus leading to spared RGC loss and the preservation of visual dysfunction. In this respect, the present compound may be viewed as a potential remedy to be added to the currently approved drug therapies for improving RGC protection.

Highlights

Glaucoma is a neurodegenerative disorder characterized by the degeneration of retinal ganglion cells (RGCs) and their axons and is the leading cause of irreversible blindness and visual impairment in developed countries, expected to affect more than 110 million people by 2040 [1]
We demonstrated that dietary supplementation with an association of forskolin, homotaurine, spearmint extract and B vitamins efficiently counteracts retinal dysfunction associated with retinal ganglion cell (RGC) death caused by optic nerve crush
We extended our investigation on the efficacy of dietary supplementation with the use of a mouse model in which RGC degeneration depends as closely as possible on intraocular pressure (IOP) elevation

Summary

Introduction

Glaucoma is a neurodegenerative disorder characterized by the degeneration of retinal ganglion cells (RGCs) and their axons and is the leading cause of irreversible blindness and visual impairment in developed countries, expected to affect more than 110 million people by 2040 [1]. Glaucoma is presently considered an age-dependent disease with pathogenetic mechanisms common to those of additional neurodegenerative pathologies of the elderly, including Alzheimer’s disease [2], with a growing incidence linked to the increasing number of people of advanced age. Visual loss is believed to be caused by RGC dysfunction associated with IOP elevation, the exact cause of RGC degeneration is still debated. There is still some debate about a causal relationship between RGC dysfunction and visual loss since RGC axon degeneration preceding neuronal loss may crucially determine the visual field impairment that characterizes glaucoma [4]. While significant RGC apoptosis has been observed in glaucoma models [5]

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