Styrene-induced changes in amacrine retinal cells: an experimental study in the rat

Dopamine (DA) is synthesized in amacrine cells and released upon membrane depolarization in a calcium-dependent way. Thus, it is recognized to function as a major neurotransmitter or modulator in vertebrate retina. Owing to DA modulating activity on cone-horizontal cells transmission, depletion or dysfunction of amacrine cells could interfere with chromatic processing, accounting for the acquired dyschromatopsia described among styrene-exposed workers. The present study has been designed to test the hypothesis that amacrine cells represent a vulnerable target of styrene in subchronically exposed rats. Ten female Sprague-Dawley rats were exposed to 300 ppm styrene 6 h/day, 5 days/week, for 12 weeks; ten rats exposed to fresh air served as a control group. Whole mounted retinas were used for the morphometry of tyrosine hydroxylase (TH) immunoreactive cells (IR). DA content and TH activity were measured by HPLC and electrochemical detection and glutathione (GSH) was measured by HPLC tandem mass spectrometry (LC-MS/MS). In treated rats, morphometric analysis showed a loss of TH-IR amacrine cells (6.2/mm2 vs. 8.7/mm2 recorded in controls, p = 0.002), without any peripheral-central variation in cell loss. DA content was also lower in exposed, as compared to control animals (208.64 vs. 267.98 microg/g w.w., p = 0.004). The activity of TH in the whole retina was similar in styrene-exposed and control rats when expressed as a function of the wet weight, whereas it was much higher in styrene-exposed rats (+64%) when expressed as a function of the number of TH-IR amacrine cells (p < 0.001). Finally, retinal GSH was reduced by 30% in exposed as compared to control rats (p = 0.01). In summary, retinal TH-IR cells were sensitive to styrene exposure, which seems to cause both structural and functional changes, represented by cell loss and DA depletion, respectively. These findings confirm the vulnerability of dopaminergic systems to styrene toxicity, providing some insights on the possible mechanism of loss in chromatic discrimination recorded among workers occupationally-exposed to styrene.