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

Dopamine (DA) is synthesized in amacrine cells and released upon membrane d epolarization in a calcium-dependent way. Thus, it is recognized to functio n as a major neurotransmitter or modulator in vertebrate retina. Owing to D A modulating activity on cone-horizontal cells transmission, depletion or d ysfunction of amacrine cells could interfere with chromatic processing, acc ounting for the acquired dyschromatopsia described among styrene-exposed wo rkers. The present study has been designed to test the hypothesis that amac rine cells represent a vulnerable target of styrene in subchronically expos ed 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 tyros ine hydroxylase (TH) immunoreactive cells (IR). DA content and TH activity were measured by HPLC and electrochemical detection and glutathione (GSH) w as measured by HPLC tandem mass spectrometry (LCMS/MS). In treated rats, mo rphometric 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 variat ion in cell loss. DA content was also lower in exposed, as compared to cont rol animals (208.64 vs. 267.98 mu g/g w.w., p = 0.004). The activity of TH in the whole retina was similar in styrene-exposed and control rats when ex pressed as a function of the wet weight, whereas it was much higher in styr ene-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 exp osed as compared to control rats (p = 0.01). In summary, retinal TH-IR cell s were sensitive to styrene exposure, which seems to cause both structural and functional changes, represented by cell loss and DA depletion, respecti vely. These findings confirm the vulnerability of dopaminergic systems to s tyrene toxicity, providing some insights on the possible mechanism of loss in chromatic discrimination recorded among workers occupationally-exposed t o styrene. (C) 2000 Inter Press, Inc.