CL SOLUTION ADDITIVE
Examining Taurine's Role in Ocular Biochemistry and in CL Wear
Find out what facts research has revealed to us about this versatile contact lens solution additive.
By J. James Thimons, OD
Taurine was first isolated from ox bile in 1827. An amino acid that isn't incorporated into proteins, taurine is involved in a host of biological and physiological functions and is a conditionally essential nutrient in humans. It's the most abundant amino acid in the ocular tissues (cornea, iris-ciliary body, lens, retina, vitreous) of rats and rabbits (Heinamaki et al 1986; Reddy 1970). According to Heinamaki's study, the mean concentration of taurine in the cornea is three times that of the next most commonly found free amino acid (taurine 10 µmol/g dry weight, aspartic acid 3.49 µmol/g dry weight). It's one of the most abundant free amino acids in the tears of normal adults (Puck et al 1984) with a reported concentration of 1.5mM (Chenzhou et al 2000). In Japan, taurine is a component of a number of eye drop solutions.
Taurine at Work
The addition of taurine to new Complete MoisturePlus multipurpose contact lens solution (Advanced Medical Optics, Inc.) enhances the buffer capacity of the solution against alkaline challenge compared to the previous, non-taurine containing formulation. The scientific literature suggests that taurine has properties that may help to protect and preserve corneal cells from hypertonic stress through osmoregulation, protein and membrane stabilization, antihistamine effects and acting as an antioxidant.
Facts on Functionality
Despite its extensive presence in ocular tissue, experts don't definitely understand the function of taurine in ocular tissues. This review covers some of the reported functions of taurine that may have relevance for the health and integrity of corneal tissues.
Evidence from animal studies shows that taurine functions as an osmoregulator and as an antioxidant in the cornea. An in-vitro experiment with immortalized human corneal epithelial cells conducted in 2002 by Shioda et al suggests that taurine increases cell viability under hypertonic stress. Researchers exposed cells to hypertonic media (450 mosmol/kg) with and without taurine supplementation at 1mM (0.0125 w/v%) for two days. They chose an osmolarity of 450 mosmol/kg because human tear film osmolarity measurements indicate that it can rise up to this value (Farris 1994). Another study reported that the osmolarity of tears measured at the front surface of a contact lens can reach 450 mosmol/kg (Benjamin 2001).
Researchers then performed a live/death assay using fluorescent stains to identify the number of live and dead corneal epithelial cells. The percent of dead cells was 2.6 percent with 1mM taurine supplementation and 4.7 percent with no supplementation. The authors concluded that taurine appears to protect human corneal epithelial cells during hypertonic stress, perhaps through an antioxidant or membrane stabilization effect. To this point, Pasantes-Morale (1985) reported that taurine may be involved in the control of lipid peroxidation in the retina and the maintenance of membrane stability.
Taurine as an Antioxidant
Koyama (Koyama et al 1996) studied taurine's role as an antioxidant in the tear film and cornea. Oxidation of cellular membrane molecules by the strong oxidizing agent hypochlorous acid (HOCl) can lead to a loss of membrane integrity and lysis of the cell. Taurine reacts with HOCl to form taurine chloramine (TauCl), a compound far less cytotoxic than HOCl. Koyama found that the addition of taurine inhibits HOCl-instigated lysis in canine red blood cells.
The authors then used lactate dehydrogenase (LDH) activity in rabbit tears as a measure of corneal irritation or damage. LDH activity increased in a dose-dependent fashion with instillation of increasing concentrations of HOCl. Taurine instilled after HOCl significantly reduced the level of LDH compared to saline instillation. Taurine instilled 30 minutes before HOCl instillation was also significantly more effective than saline at reducing the levels of LDH activity. The authors of the study suggest that "taurine may be clinically useful in the treatment of ocular surface damage caused by oxidants such as HOCl."
Other Roles for Taurine
Animal studies of non-ocular tissues have also implicated taurine in protein stabilization, protection against lactic acidosis, pain perception and modulation of the inflammatory response pathway. In-vitro studies have shown that taurine can act to stabilize proteins against thermal denaturation. Arakawa and Timasheff (1985) looked at the course of heat denaturation on lysozyme in the presence or absence of taurine and a variety of other osmotic regulators. Taurine proved to be the most effective additive in stabilizing lysozyme against thermal denaturation. Experts believe that protein denaturation enhances lysozyme binding to contact lenses. Thus, inhibition of protein denaturation may decrease protein binding, such as to contact lenses.
In the central nervous system, taurine protects cells against hypoxia and lactic acidosis. Nakada reported that high levels of cytosolic taurine buffer brain cells against lactic acidosis induced by anoxia and hypoxia (Nakada, 1991, 1992). Lactic acidosis within the stroma and epithelium of the cornea causes adverse events for contact lens wearers (Bonnano et al 1987). Unfortunately, we need more cornea-specific studies to ascertain whether exogenous taurine could minimize lactic acidosis in contact lens wearers.
In rodents, taurine acts to diminish pain responses for a variety of standard nociception tests (tail flick, hot-plate, acetic acid test). Researchers initiated a pain response (writhing) in mice with intraperitoneal injection of 0.6 percent acetic acid. Pretreatment by intraperitoneal injection of taurine decreased the pain response in a dose-dependent fashion (Serrano et al 2002). The mechanism for this action is unknown, but appears to involve several neurotransmitter systems.
Taurine decreased the inflammatory response in rat gastrointestinal cells. In a model of gastric mucosal damage, taurine decreased histamine release in acid-perfused stomachs of rats (Hung and Hung 1999). Taurine also significantly reduced the release of histamine from intestinal epithelial cells in response to laural sulfate, a drug absorption enhancer that is also cytotoxic (Endo et al 2002). In both systems, taurine acted as a cytoprotectant. Part of the cytoprotective effect of taurine may result from its ability to decrease the release of histamines, interrupting the inflammatory pathway (Hung and Hung 1999; Endo et al 2002).
Histamine release causes the classic clinical symptoms of allergic ocular conjunctivitis Type I allergy, itching and tearing. Tears from asymptomatic and symptomatic contact lens wearers have significant levels of histamine, although a clear correlation between histamine levels and adverse ocular responses during contact lens wear is lacking (Tan et al 1997).
As part of a clinical evaluation of several multi-purpose contact lens solution formulas, researchers tested two formulas that were identical except for the inclusion of taurine with a concomitant change in the level of phosphate buffer included. Solution 1 didn't contain taurine and solution 2 contained 0.05 percent taurine.
Over the course of a 90-day testing period, there were no differences between the groups in measures of patient comfort or visual acuity. However, researchers did note differences for the discomfort symptoms of excessive tearing and itching. In both cases, the symptoms were greater for the group using the solution without taurine (Table 1).
Reaching a Better Understanding
The role of taurine in the cornea and the effect of its addition to a multipurpose contact lens solution requires continued research. Investigators have demonstrated a role for taurine as an antioxidant and osmoregulator in animal studies of corneal tissue. Animal studies of non-ocular tissues have documented roles for taurine in protein stabilization, protection against lactic acidosis, pain perception and histamine release.
Overall, taurine seems to play a role in homeostasis at the cellular level, acting to preserve the integrity and viability of cells exposed to a variety of environmental stressors.
To obtain references for this article, please visit http://www.clspectrum.com/references.asp and click on document #104.
Dr. Thimons is a nationally and internationally acclaimed speaker and serves as medical director of Ophthalmic Consultants of Connecticut. He was awarded Optometry's Top Educator in 1999 and is a member of Advanced Medical Optics' Advisory Board.