Antioxidant Saffron and Central Retinal Function in ABCA4-Related Stargardt Macular Dystrophy.

Marco Piccardi,Angelo M Minnella,Francesco Martelli,Matteo Bertelli,Adriano Magli,Benedetto Falsini,Dario Marangoni,Silvia Bisti,Stefano Di Marco,Antonello Fadda

doi:10.3390/nu11102461

Abstract

Retinal oxidative damage, associated with an ATP-binding cassette, sub-family A, member 4, also known as ABCA4 gene mutation, has been implicated as a major underlying mechanism for Stargardt disease/fundus flavimaculatus (STG/FF). Recent findings indicate that saffron carotenoid constituents crocins and crocetin may counteract retinal oxidative damage, inflammation and protect retinal cells from apoptosis. This pilot study aimed to evaluate central retinal function following saffron supplementation in STG/FF patients carrying ABCA4 mutations. Methods: in a randomized, double-blind, placebo-controlled study (clinicaltrials.gov: NCT01278277), 31 patients with ABCA4-related STG/FF and a visual acuity >0.25 were randomly assigned to assume oral saffron (20 mg) or placebo over a six month period and then reverted to P or S for a further six month period. Full ophthalmic examinations, as well as central 18° focal electroretinogram (fERG) recordings, were performed at baseline and after six months of either saffron or placebo. The fERG fundamental harmonic component was isolated by Fourier analysis. Main outcome measures were fERG amplitude (in µV) and phase (in degrees). The secondary outcome measure was visual acuity. Results: supplement was well tolerated by all patients throughout follow-up. After saffron, fERG amplitude was unchanged; after placebo, amplitude tended to decrease from baseline (mean change: −0.18 log µV, p < 0.05). Reverting the treatments, amplitude did not change significantly. fERG phase and visual acuity were unchanged throughout follow-up. Conclusions: short-term saffron supplementation was well tolerated and had no detrimental effects on the electroretinographic responses of the central retina and visual acuity. The current findings warrant further long-term clinical trials to assess the efficacy of saffron supplementation in slowing down the progression of central retinal dysfunction in ABCA4-related STG/FF.

Highlights

Stargardt disease (STG) is the most common hereditary recessive macular dystrophy [1]characterized by juvenile to young adult onset, central visual impairment, progressive bilateral atrophy of the macula and retinal pigment epithelium (RPE), with a frequent appearance of orange/yellow flecks distributed around the macula and/or the mid retinal periphery [2]
In vitro studies [7] demonstrated that the ABCR itself is an efficient target of all-trans-retinal-mediated photo-oxidative damage
ERGs were elicited by the LED-generated sinusoidal luminance modulation of a circular uniform field, presented at the frequency of 41 Hz on the rear of a Ganzfeld bowl uniformly illuminated at the same mean luminance as the stimulus. focal electroretinogram (fERG) were recorded monocularly using Ag-AgCl superficial cup electrodes taped over the skin of the lower eyelid

Summary

Introduction

Stargardt disease (STG) is the most common hereditary recessive macular dystrophy [1]characterized by juvenile to young adult onset, central visual impairment, progressive bilateral atrophy of the macula and retinal pigment epithelium (RPE), with a frequent appearance of orange/yellow flecks distributed around the macula and/or the mid retinal periphery [2]. A clinically similar retinal disorder, fundus flavimaculatus (FF), often displays later ages of onset and slower progression. It has been suggested and demonstrated [3] that STG and FF represent allelic disorders. The ABCR gene is expressed at high levels in the retina, in both rod and cone photoreceptors [4]. Accumulation within the RPE cells of a compound, A2E, forming from the condensation of phosphatydilethanlolamine (PE) and the all-trans-retinal released from photoactivated rhodopsin [6], probably leads in vivo to increased absorption of blue lights and phototoxic RPE cell damage. The mutation-induced disease may affect both rod and cone photoreceptors, at relatively early stages. In vitro studies [7] demonstrated that the ABCR itself is an efficient target of all-trans-retinal-mediated photo-oxidative damage

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