| Retina ganglion cell(RGCs),located in inner layer of the retina, which are important efferent neurons of visual sigual.Changes of form and function of the RGCs will inevitably lead to vision dysfunction. Retina injury caused by hypoxia, such as glaucoma, diabetic retinopathy, central retinal artery occlusion, etc. often have certain influence on RGCs. This is a clinically common kind of retinal disease of great harm, therefore, finding effective treatments is a urgent task.The mechanism of hypoxic damage to RGCs is still unknown. RGCs have some kind of self-protection under acute hypoxia circumstances. Adaptation to hypoxia is an important pathway to hypoxia.Enhanced hypoxia inducible factor 1 (HIF-1),the self regulating factor of hypoxia adaptation adaptation is effective for hypoxia reaction. It was specificity and susceptivity to hypoxia signals and its catholicity of existing in organizations and target gene regulation, is the most important core transcription factor in the regulation of genes related to hypoxia. HIF-1 can regulate target gene related to the production of erythrocyte, angiogenesis, energy metabolism, hormone metabolism, etc, underlining the adaptive ability of organizations to hypoxia. Therefore, it is of great significance to strengthen the expression of HIF-1 in hypoxia circumstance to protect neuron.Neuroglobin(Ngb) is a kind of grade ischemic induced nervous tissue protein, mainly existing in retina and brain. Its inducing effect is related to transduction ways of hypoxia signals. Researches have found that Ngb can improve tolerance of nerve cells to hypoxia, at the mean time, hypoxia circumstance can otherwise strengthen the expression of Ngb. The exact mechanism is still unknown, may be it is a receptor that can regulate the rate of O and NO, or it can improve the anti-oxidation ability by strengthen the expression of antioxidase. Ngb is a kind of hypoxia reaction gene (HRG) induced by HIF-1, and one of the downstream controlling genes of HIF-1. Past researches have found that, several segment of sequence 5'-RCGTG-3'combined with HIF-1 exist in the Ngb5'–end noncoding region, this can at the same time improve the transcription of Ngb genes, strengthen the expression of Ngb, and be favorable for neurons to get enough oxygen in hypoxia circumstance and satisfy the need of its function.Taurine (Tau) is the most abundant free aminoacid in retina, which is a multifunctional agents. Taurine is not only a determinative factor in early stage differentiation of retina, but also something that take part in the formation of vision as a suppressed neurotransmitter. More over, it can maintain normal function of vision by regulating the balance of osmotic pressure in and out of cells, balance of factor IV calcium, antopxidation and taking part in membrane phospholipid metabolism and stabilizing membrane system. Research done by Chenfang has confirmed that taurine can improve the adaptation of retina to hypoxia by activating upstream and downstream genes in HIF access, therefore, we presume that taurine can improve the adaptation of RGCs to hypoxia circumstance by way of HIF-1/Ngb, maintain its normal physiologic function, thus effectively prevent harm to RGCs in hypoxia circumstance.Based on the analysis above, we presume taurine maybe an effective protective agent of retina damage induced by hypoxia. This project plans to look into the protective effect and mechanism of taurine to RGCs harm in hypoxia circumstance by using it to intervene RGC-5. RGC-5 is an immutalizing cell strain of rats, belongs to undifferentiated juvenile cells. Compared to primary culture RGCs, it only lacks electrophysiology characteristic, thus it is already widely used in lab researches in recent years. This experiment will first set up a hypoxia RGC-5 model, and make further intervention with different dose of taurine, and will for the first time observe the influence of taurine to RGC-5 in hypoxia circumstance and study its preventative effect through lab techniques of amino acid analysis, laser confocal analytic technique,flow cytometry, RT–PCR, and western blottingmethod etc. It will also make intensive probe into possible molecular mechanism of protective effect of RGCs in hypoxia circumstance. The main results and conclusions were summarized as follows:1. The cell viability of RGC-5 cells under hypoxia,decreased apparently, the released LDH activities elevated and apoptosis clearly activities.Taurine can effectively reinforce the viability of RGCs under hypoxia and degrade Apoptosis. Taurine could partially protect RGCs against hypoxic injury.2. The content of NO,GSH in the hypoxia group is apparent lower than the normoxia group (P<0.05), while the content of MDA has dramatically raised; after the intervention of taurine, the content of NO,GSH can significantly increased(P<0.05), while the content of MDA significantly dropped(P<0.05). The above results suggest that taurine has strong protective effect, maybe because it can eliminate a lot of radicals effectively, restrict lipid peroxidation and enhance anti oxidant function, thus protect RGCs.3. In vivo studies confirmed that HIF-1 and Ngb participated the hypoxia adaptation of RGCs. HIF-1αmRNA and proteins rise rapidly to the peak, tauine can promote the express of HIF-1αmRNA and proteins, which can help HIF-1 influence RGCs constantly and promote the hypoxia adaptation. Ngb mRNA and protein express a little at the early stage of hypoxia,but expression of taurine treatment.This experiment has proved that taurine can improve the hypoxiz adaptive regulation of RGCs and therefore reduce RGCs harm.In summary, hypoxia harm can cause changes to RGCs'morphological structure and feature protein. The treatment of taurine has obvious protective effect to RGCs hypoxia harm, which perhaps related to taurine raise activity of antioxidase, regulate HIF-1 and its downstream gene Ngb's transcription expression. The result of this experiment will provide experiment basis for using taurine to prevent retina harm caused by hypoxia.
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