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Am J Neurodegener Dis 2013;2(3):208-220

Original Article
The time course of action of two neuroprotectants, dietary saffron and
photobiomodulation, assessed in the rat retina

Fabiana Di Marco, Stefania Romeo, Charith Nandasena, Sivaraman Purushothuman, Charean Adams, Silvia Bisti,
Jonathan Stone

Department of Biotechnology and Applied Clinical Science, University of L’Aquila, Italy; Discipline of Physiology and
Bosch Institute, University of Sydney and ARC Centre of Excellence in Vision Science, University of Sydney, Australia

Received June 19, 2013; Accepted August 5, 2013; Epub September 18, 2013; Published September 30, 2013

Abstract: Background: Dietary saffron and photobiomodulation (low-level infrared radiation, PBM) are emerging as
therapeutically promising protectants for neurodegenerative conditions, such as the retinal dystrophies. In animal
models, saffron and PBM, given in limited daily doses, protect retina and brain from toxin- or light-induced stress. This
study addresses the rate at which saffron and PBM, given in daily doses, induce neuroprotection, using a light damage
model of photoreceptor degeneration in Sprague Dawley (SD) rats. Results: Rats were raised in dim cyclic (12 h 5 lux,
12 h dark) illumination, treated with saffron or PBM for 2-10 d, and then exposed to bright damaging light (1,000 lux for
24 h). After 1 week survival, the retina was assessed for photoreceptor death (using the TUNEL reaction), for surviving
photoreceptor damage (thickness of the outer nuclear layer) and for the expression of a stress-related protein GFAP,
using immunohistochemistry. Preconditioning the retina with saffron or PBM reduced photoreceptor death, preserved
the population of surviving photoreceptors and reduced the upregulation of GFAP in Müller cells. At the daily dose of
saffron used (1 mg/kg), protection was detectable at 2 d, increasing to 10 d. At the daily dose of PBM used (5 J/cm2 at
670 nm) protection was detectable at 5 d, increasing to 7-10 d. Conclusions: The results provide time parameters for
exploration of the mechanisms and durability of the protection provided by saffron and PBM. (AJND1306003).

Keywords: Saffron, photobiomodulation, retinal degeneration, neuroprotection, light damage

Address correspondence to: Dr. Jonathan Stone, Department of Physiology and Bosch Institute, University of Sydney
F13, NSW 2006 Australia. Tel: 61 2 9351 4740; Fax: 61 2 9351 6470; E-mail: jonathan.stone@sydney.edu.au