Abstract

The eye is amazing in its ability to maintain living tissues in an exposed environment in a transparent state. The cornea and lens must not only be clear but also maintain precise shapes to focus images on the retina. For animals living in both aquatic and terrestrial environments the problems are magnified. The cornea uses special structural molecules of precise size and arrangement to keep from scattering light. This structure is maintained by remaining relatively dehydrated due to active transport in the cells of the endothelium lining the inside of the cornea (these are a true epithelial monolayer). This requires a constant energy supply for the epithelial cells to maintain the pumps. Similarly the lens must maintain a constant state of hydration requiring active processes. Problems in these active processes can be perceived as haziness or opacity of these tissues.¹

Another factor increasing the sensitivity of the eye to environmental conditions is the lack of direct blood supply to these active tissues. Movement of glucose and oxygen to these cells and waste products away from them requires diffusion and transport through the aqueous humor. Even the conjunctiva under the eyelids and around the eye is a very specialized tissue. It has minimal keratinization and abundant blood vessels very close to the surface. It more closely resembles the mucosal surfaces of the respiratory or digestive systems than skin. It is closely integrated in its circulation with the aqueous flow from the eye.⁴

Oxidizing agents including chlorine, ozone, bromine and ultraviolet light are commonly used as disinfectants to maintain clarity, and reduce microscopic organisms in life support systems for marine mammals. These compounds can cause injury by themselves if in too high a concentration. Interaction of these agents with compounds dissolved in the water produces by-products of disinfection. The compounds produced are not commonly measured and cannot all be measured with the same techniques so their concentration and identification are not usually known. Presence of bromine in incoming water or its use as a disinfectant can significantly change the compounds produced and their rate of production.^3,6 Chlorination of water with even a small amount of bromine can produce bromate levels higher than the drinking water limit of 10 ppb.

Some of these by-products of disinfection are volatile and can be absorbed by inhalation or penetration of tissues.^1,5 Safe levels for human drinking water are based on drinking 2 liters of water daily and taking one short shower or bath.⁸ Our animals are in or near the water 24 hours a day.

The simplest compounds of interest include the halogenated methanes including chloroform, bromodichloromethane, dibromochloromethane, and bromoform. These compounds have been shown to be toxic to liver and kidney and the mechanism of toxicity involves initial oxidation by cytochrome p450 enzyme systems.^2,5 For chloroform the initial oxidation produces an unstable product that breaks down to carbonyl chloride ( CCl₂O ) and HCl. Carbonyl chloride is very reactive binding with and damaging any molecule it contacts or even with water to produce CO₂ and 2 HCl. Carbonyl chloride is also known as phosgene and has been associated with industrial accidents and has been used as a poison gas. Damage comes from either the phosgene or the resulting 3 molecules of HCl. Glutathione can bind to the carbonyl chloride and prevent it from reacting with other compounds and glutathione levels are lowered in experimental models of its toxicity. Other compounds may also produce similar toxic compounds after cytochrome p450 activation.

All cells use similar energy producing pathways and mechanisms to handle damaging intermediates. For example the cytochrome p450 system enzymes which act to begin the breakdown of drugs or toxins are present in ocular tissues (specifically the ciliary body) at about 5% of the concentration in liver cells.⁴ Antioxidant compounds and systems are very important in handling free radicals, peroxide and other damaging intermediates resulting from the activity of these cytochrome systems. A reducing environment is important in the cell. Oxidation is the enemy of living tissues. Glutathione is one of the important protective compounds. It binds to free radicals and then in an energy-requiring step is regenerated to continue its protective function. "When the intracellular levels of glutathione are reduced in the cornea by one-third, the clarity of the cornea and its ability to pump fluid declines dramatically."⁴

Light, especially UVA and short wave length blue light, can also produce oxidizing intermediates which must be handled by glutathione. UVA light increased the cytochrome p450 levels in a tissue culture model of UVA injury to skin cells.⁷ The effects of ultraviolet light and toxic compounds would be additive.

Oxidizing compounds reacting with phospholipids in cell membranes producing secondary messenger compounds such as arachidonic acid feed the arachidonic acid cascade system to produce prostaglandins, leukotrienes and a host of down-stream compounds. This likely plays a role in uveitis.

Measures to reduce by-products of disinfection could include reducing oxidant levels, measuring bromine levels in source water, reducing precursors such as dissolved organic carbon and nitrogenous wastes, and improved ventilation. Measuring by-product levels would be valuable and monitoring the relationship of eye health and these compounds could confirm or refute their importance.

References

1.  Aggazzaotti G., et al. 1990. Plasma chloroform concentrations in swimmers using indoor swimming pools. Arch Env Health 45: 175-179.

2.  Bailie M.B., J.H. Smith, J.F. Newton, and J.B. Hook. 1984. Mechanism of chloroform nephrotoxicity. IV. Phenobarbital potentiation of in vitro chloroform metabolism and toxicity in rabbit kidneys. Tox Appl Pharm 74(2): 285-292.

3.  Chang E.-E., P.-C. Chiang, J.-T. Liu, I.-S. Li, and S. H. Chao. 2008. Effect of bromide and ammonia on the formation of ozonation and chlorination by-products. Pract Periodical Haz Toxic Radioactive Waste Mgmt 12: 79-85.

4.  Forrester J.V., A.D. Dick, P.G. McMenamin, W.R. Lee. 2002. The Eye: Basic Sciences in Practice, 2^nd Edition. Elsevier Health Sciences, ISBN 0702025410, 9780702025419.

5.  Pohl L., J. Gorge, and H. Satoh. 1984. Strain and sex differences in chloroform induced nephrotoxicity. Different rates of metabolism of chloroform to phosgene by the mouse kidney. Drug Metab Disp 12(3): 304-308.

6.  Sohn J., G. Amy, and Y. Yoon. 2006. Bromide ion incorporation into brominated disinfection by-products. Water Air Soil Poll 174: 265-277.

7.  Svobodova A., D. Walterova, J. Vostalova. 2006. Ultraviolet light induced alterations to the skin. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 150(1): 25-38.

8.  Trihalomethanes in Drinking-water. Background document for development of WHO Guidelines for Drinking-water Quality. WHO/SDE/WSH/05.08/64 2005.

9.  Young, S. Personal communication, Vancouver Aquarium, Vancouver, British Columbia, Canada.