The Expression Of PirB And Its Role In The Developing And Injured Visual Pathway Of BALB/c Mice

Myelin-associated inhibitors in central microenvironment play a vital role in the failure of axonal regeneration of adult mammalian central neurons. Previous studies showed three major inhibitors Nogo-66, MAG, OMgp all bound NgR to inhibit axonal regeneration. However, many studies, including our previous work, revealed the regenerate ability of central neurons axonal was still limited with the absence of NgR. In recent issues of《Science》and《Neuron》,a second receptor for these myelin inhibitors was described, PirB, to which the three major inhibitors could also strongly bind inhibit axonal regeneration. It was also reported PirB might play a more important role than NgR in axonal regeneration inhibition of central neurons.PirB was first discovered in immune system, and identified as those homologous to human Fc receptor (FcR) for immunoglobulin A (IgA), FcaRI. PirB is expressed on various haematopoietic cell lineages. PirB can prevent the immune cells injuring the normal human cells, which is realized by regulating integrin and Ca2+ signaling and changing cytoskeletal dynamics and cellular adhesion. In the immunologic system, PirB plays a vital role in regulating the balance of immune function.The expresssion of PirB in central neurons was first confirmed by Josh Syken et.al in 2006. They foud that Specific PirBmRNA and protein signal was detected throughout the mice brain at all ages tested. Functional experiments demonstrated that PirB was crucial for the axonal guidance and plasticity of central neurons, and might function to stabilize neural circuits. However, does optic nerve (ON) as a member of CNS express PirB? Our previous work discovered that:1,By using intravitreal NgRsiRNA injection to remove the function of NgR gene, the injured ON and RGCs could get partly regeneration, which suggested some other mechanism inhibitting the regeneration of ON might exist.2,The expression of NogoA was obviously increased after ON injury, but its receptor NgR did not change at all. The expression of NgR was not consistent with its ligand NogoA. Dose it suggest NogoA might bind other receptor to inhibit ON regeneration after ON injury? Is PirB the new receptor?The study is divided into three parts: 1. The expression and the position of PirB in normal nerve tissue (including visual pathway) of adult BALB/c mice; 2. The expression of PirB and its role in the developing visual pathway of BALB/c mice; 3.The expression of PirB and its role in the visual pathway of adult BALB/c mice after ON injury.The main results and conclusions are as follows:1. The expression of PirB is positive in retina, optic nerve, visual cortex, cerebellar and spinal cord and is Negative in sciatic nerve. The level of PirB protein expression is higer in visual cortex and lower in optic nerve. PirB protein is widely expressed in central nerve tissues, but not expressed in peripheral nerve. It suggests the positive expression and position of PirB may play a vital role in the poor ability of CNS regeneration.2. The positive expression of PirB was discovered in the visual pathway in the time of birth. It was found in retina, optic nerve and visual cortex during all postnatal development. The expression of PirB increased with age. Our previous work showed the expression of NogoA, the PirB ligand, decreased with age. That the expression of PirB was not consistent with NogoA suggest NogoA-PirB Signaling pathway may be similar with NogoA-NgR pathway, for its function not only inhibits axonal regeneration but also takes part in the development, axonal guidance and plasticity of central neurons in some case.3. The improved ON clamp model of adult BALB/c mice was successfully established based on our previous SD rats ON clamp model, which made a good foundation for the further mice experiments.4. At day 1 after ON injury, the expression of PirB in the injuried visual pathway was significantly increased, nearly peaked at day 7, and still maintained at a high level at day 28. Our previous work demonstrated that NogoA expression was obviously increased at day 3 after ON injury, and still maintained a high level at day 25, but no change of NgR. So, both the expression of NogoA and PirB were up-regulated, but NgR had no change after ON injury. The results suggest PirB may be a more critical molecule than NgR in axonal regeneration inhibition after ON injury.