The Protective Effect And Mechanism Of Taurine On Photochemical Damage In Rat Retina

As the retina has evolved especially to be sensitive to light, retina photic injury is often induced by prolonged or intense light exposure. Retina photic injury includes thermal damage, photodisruption damage and photochemical damage, among which the latter is particularly prevalent. The declined visual function and disintegrated retina outer/inner segment (ROS/RIS) occurs in the early phase of photochemical damage, and then photoreceptor degeneration or even apoptosis ensues, outer nuclear layer (ONL) turns to be thinner, eventually the retina endangeres to totally lose function or even to blindness.Recent researches have proved that apoptosis of photoreceptor is the final pathway in in retinitis pigmentosa (RP), age-related macular degeneration (ARMD) and photochemical damage, now, apoptotic mechanisms are summarized as follows: (1) Induction-phase: the chromophore, rhodopsin, retinoids mediate photon absorbing; (2) The early phase of death-signal transduction: calcium overload, mitochondria damage, lipid peroxidation and reactive oxygen intermediates (ROI) may play important roles in initiating light damage;(3) The late phase of death-signal transduction:activator protein-1 (AP-1) triggers the apoptoic pathway and c-fos (subunit of AP-1) was identified to be the essential factor in photochemical damage; the decreased activity of NFkB has been proved to be related to light damage;(4) Termination phase: DNA fragmentation depends not only on Caspases but also Cathepsin, Calpains, Granzymes A/B etc; clearance of the cell-debris is executed by the macrophages and retina pigment epithelia. Agents, such as calcium antagonist, antioxidants, dexamethasone and neurotrophic factors, have been proved to be neuroprotective, but the potential toxity and inconvinience make them not fit to be the routine neuroprotective agents.which call for new drugs with no side-effects, be convenient and health-promoting.Taurine, abundant in retina especially in photoreceptor cells and muller cells, plays important roles in retinal growth and development process and maintaining normal visualfunction. Recent researches have found taurine as a free radical quencher, and taurine can inhibit lipid peroxidation in Galactose catarat, diabetes retinapathy etc. Other studies have found the anti-apoptotic effect of taurine in cerebellum neurons, retina pigment epithelium cell. In short, we presume that taurine may have protective effect in photochemical damage.According to the analysis above, our study was determined to observe whether dietary supplementation with taurine had protective effect in experimental photochemical damage and further explore the probable mechanism. First, SD rats, fed with 2% or 4% taurine, were exposed to damaging light, and then retina function and morphology changes were examined to evaluate the protective action. Secondly, the products of lipid-peroxidation and activity of anti-oxidases were examined to elucidate correlations between taurine and oxidation. Meanwhile, some important and peculiar transducers of the death sigal pathway were investigated by RT-PCR, immuno-histochemistry and western-blot analysis to evaluate molecular mechanism.The main results and conclusions are summarized as follows:1. After 3000±2001x, 24h cool white light exposure, ROS/RIS were in disorder and ONL got thinner (from 12-15 layers to 4-7 layers) , which indicated photochemical damage model had been successfully established.2. Retina function was decteced by ERG After exposure, decreased a/b amplitude (Aa /Ab) and prolonged a/b latent time (La/Lb) were found in control group, but in taurine group especially in 4% taurine group ERGs remained typical. Using light /transmission electron microscopy, slight disorganized ROS/RIS and little swollen mitochondria and lysosome were found in taurine group after 24h exposure. These findings demonstrated that dietary supplementation with taurine, particularly in 4% dose, partly protected photoreceptors from degeneration.3. The Apoptotic index (AI), positively correlated with light-exposure time, was reduced in taurine group in respective exposure time point, among which AI of 12h exposure in taurine group (12.3+4.7 %) was significantly lower than the control(32.4 ± 6.2%). These results implied the anti-apoptotic effect of taurine in photochemical damage.4. As light exposure time prolonged from Oh to 24h, the MDA content in rat retina increased dramatically, but in taurine group (54.62 ± 13.07 mmol/g) of 24h-exposure it was relative low when compared with the control (98.10+11.75 mmol/g) (p<0.05). In earlyphase (3h> 6h) of light exposure, the activity of SOD was elevated especially in taurine group(165.27± 10.09 IU/g, Control 132.56+9.94 IU/g); Similarly, after 6 hour's exposure the GSH-Px activity reached to its peak, the taurine group (54.36 + 6.11 nmol/g.min) was higher than the control (46.29 + 3.42 nmol/g.min) .The above indicated through inhibiting peroxidation and elevating anti-oxidase activity, taurine palyed an important role in keeping the retina away from light damage.5. As early as lh after lights on, c-fos mRNA was transiently induced, which was further identified as the results of the abnormal c-fos expression in ONL, and the other important subunit c-jun was induced at 6h and persisted in high levels, but in taurine group these were relative low so that AP-1 formation may be partially inhibited. In taurine group the nuclear p65 content was higher than control and IicBa mRNA ( a target gene of NFkB ) was highly induced at 3h/6h, which indicated the elevated activity of NFkB. Caspase-1 did not increase until after 6h exposure while in tarine group it was detected at 9h and the amount of Caspase-1 was makedly decreased. These showed taurine had great influences on the above regulators and further inhibited death signal transuduction.Above all, our studies suggested that taurine played neruoprotective role in photochemical damage, which might associate with its anti-peroxidation and inhibition of death signal tranduction through adjusting AP-1, NFkB and Caspase-1 expression.