Abstract
Retinal pigment epithelium (RPE) provides nourishment and protection to the eye. RPE dysfunction due to oxidative stress and inflammation is one of the major reason for many of the retinal disorders. Organophosphorus pesticides are widely used in the agricultural, industrial and household activities in India. However, their effects on the eye in the context of RPE has not been studied. In this study the defense of the ARPE19 cells exposed to Chlorpyrifos (1 nM to 100 µM) in terms of the enzyme paraoxonase (PON) was studied at 24 hr and 9 days of treatment. Chlorpyrifos was found to induce oxidative stress in the ARPE19 cells as seen by significant increase in ROS and decrease in glutathione (GSH) levels without causing cell death. Tissue resident Paraoxonase 2 (PON2) mRNA expression was elevated with chlorpyrifos exposure. The three enzymatic activities of PON namely, paraoxonase (PONase), arylesterase (PON AREase) and thiolactonase (PON HCTLase) were also found to be significantly altered to detoxify and as an antioxidant defense. Among the transcription factors regulating PON2 expression, SP1 was significantly increased with chlorpyrifos exposure. PON2 expression was found to be crucial as ARPE19 cells showed a significant loss in their ability to withstand oxidative stress when the cells were subjected to chlorpyrifos after silencing PON2 expression. Treatment with N-acetyl cysteine positively regulated the PON 2 expression, thus promoting the antioxidant defense put up by the cells in response to chlorpyrifos.
Highlights
Retinal pigment epithelium (RPE) is a monolayer of epithelial cells between the neural retina and the choriocapillaris [1]
Cell viability assay The ARPE19 cells were treated with varying concentration of Chlorpyrifos (1 nM to 100 mM) for 24 hr and 9 days
reactive oxygen species (ROS) generated as an index of oxidative stress ARPE19 cells exposed to chlorpyrifos (1 nM to 100 mM) for 24 hr induced a significant increase in ROS production even at 1 nM chlorpyrifos (p,0.05) (Figure 1.C)
Summary
Retinal pigment epithelium (RPE) is a monolayer of epithelial cells between the neural retina and the choriocapillaris [1]. RPE cells act as a selective barrier in regulating the movement of nutrients and solutes from the choroid to the sub-retinal space forming the outer blood-retinal barrier [2]. Pesticides like paraquat are reported to induce oxidative damage to the RPE [6]. Organophosphate insecticide, Chlorpyrifos (CPF; O,O-diethylO-(3,5,6-trichloro-2-pyridyl) phosphorothioate) is common in agricultural, industrial and household pesticide formulations [7,8]. It is classified by WHO as class II moderately hazardous compound that has an LD50 range of 20–2000 mg//kg body weight in rat [9]. Abnormal electroretinograms were noticed in rats after administration of chlorpyrifos [12]
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