Superfund Research Program

The Effects of Organophosphate Compounds on the Developing Eye

Release Date: 02/24/1999

Organophosphate compounds were tentatively linked to visual disorders in the 1960s, when Japanese researchers noted an increased incidence of myopia, astigmatism, and other ocular problems in residents of Japan's Saku region, an agricultural area where organophosphate pesticides were extensively applied. More recent experimental studies with animal models demonstrate numerous effects of organophosphate compounds on the visual system. Now some scientists are beginning to question whether this group of compounds is capable of affecting the eye during its sensitive period of development.

Researchers at the University of California-Davis recently reported that the organophosphate insecticide, diazinon, impaired the development of the retina in medaka (Oryzias latipes), a fish model that is increasingly being used for studies of environmental and human health. In control embryos, the retina differentiated into three distinct cellular layers. However, in embryos exposed to diazinon, the retina showed no cellular differentiation. Exposed embryos also had a dramatic increase in necrosis within the retina.

These researchers also investigated the possible biological mechanisms underlying the retinal toxicity observed in medaka embryos. Because many of the toxic properties of organophosphate compounds are mediated by their ability to inhibit the enzyme, acetylcholinesterase (AChE), the scientists investigated whether development of necrotic lesions in the medaka retina was correlated with AChE inhibition. AChE normally catalyzes the breakdown of the neurotransmitter acetylcholine.

The investigators discovered that, in diazinon exposed embryos, inhibition of retinal AChE occurred at the same time increasing numbers of necrotic lesions were forming in the retina, suggesting the two events were related. However, the researchers also noted that, in addition to AchE inhibition, other factors were likely involved in producing retinal necrosis. The researchers have proposed some possible mechanisms that may be involved in producing retinal cell death and they plan further studies "to shed mechanistic information on toxic responses within developing vertebrate retina."

The retina plays a crucial role in vision. Located at the back of the eye, the retina receives the image formed by the lens and conveys information to the brain through the optic nerve. This important component of the eye also contains the rod and cone cells that are responsible for perceiving light and color. Therefore, any damage involving the retina constitutes a serious threat to vision.

In light of what is already known about the effects of organophosphates on the eye in humans and rodent models, the results of this current study suggest the need for further research regarding the potential for organophosphates to induce retinal toxicity in developing organisms.

Organophosphate insecticides represent a group of compounds to which humans are widely exposed. In addition to being present as residues in our food supply, organophosphate insecticides are used around the home to exterminate indoor pests and to control insects in gardens. Insecticide residues around the home are a significant source of exposures to pregnant women who, with developing child, are uniquely sensitive to such exposures.

Wildlife are also highly susceptible to organophosphate insecticide exposures. In the United States, approximately two-thirds of the insecticide treatments on cropland involve organophosphate insecticides. Although intended for specific insects in specific locations, these agricultural chemicals often drift onto surrounding areas of land and sometimes even migrate into streams, rivers, and other bodies of freshwater, exposing many non-target organisms to the compounds including birds, fish, aquatic insects, and other beneficial organisms.

This research is significant for increasing our understanding of the ocular and developmental toxicity of organophosphate compounds. Because many stages of development in the medaka fish model have been characterized - including development of the eye - and some developmental stages are conserved among vertebrate groups, these results can help clarify the possible linkages between organophosphates and visual toxicity in developing vertebrates, including humans.

For More Information Contact:

D E Hinton
University of California-Davis

To learn more about this research, please refer to the following sources:

• Hamm JT, Wilson BW, Hinton DE. 1998. Organophosphate-induced acetylcholinesterase inhibition and embryonic retinal cell necrosis in vivo in the teleost (Oryzias latipes). Neurotoxicology 19(6):853-870. PMID:9863774

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