| Traumatic optic neuropathy(TON)is the direct or indirect injury to the optic nerve caused by head or face trauma,which often causes severe damage to visual function,accounting for about 2%-5% of closed head injury.The mechanism of TON is not yet fully understood.At the present time,it is believed that the mechanism includes primary optic nerve injury,and secondary injury which caused by vascular diseases and inflammation.Research has shown that the apoptosis of ganglion cells reaches the peak level about 7 days after optic nerve injury,and the mechanism of RGCs apoptosis may be related to the axonal injury,the obstacle of axoplasmic transport and lack of nutritional factors or nutritional support.Owe to the complicated pathogenesis of TON,there is still no effective treatment.The current treatment includes conservative treatment,corticosteroid therapy,optic canal decompression and combined therapy.Although corticosteroid therapy and optic canal decompression have a certain effect in some cases,the effect is not good,especially for patients with no light perception and light perception.Although optic canal decompression can relieve the compression of the injured area,it still cannot change secondary injuries such as optic nerve edema,inflammation,ischemia,excessive activation of glutamate receptors,lipid peroxidation,and calcium overload which eventually lead to the formation of glial scars on neurons as well as the apoptosis of RGC cells.Therefore,there is an urgent need for a new treatment strategy for TON.Optic canal decompression is currently the most important surgical method for TON.It is primarily used to remove the bone around the optic canal through surgery,so that release the oppressive symptoms of the optic nerve caused by edema and hemorrhage after the optic canal,thereby alleviating the blood flow disorder of the optic nerve.Currently,the most common used optic canal decompression is endoscopic transnasal optic canal decompression.Traditional transnasal optic canal decompression is performed by removing the anterior and posterior ethmoid sinuses and sphenoid sinus from the uncinate.This approach is easy to operate under the wide field vision of the optic canal.However,the disadvantage is that the iatrogenic damage is relatively large,and the anatomical structure of the ethmoid sinus is further complicated.Moreover,it is easy to destory the cranial tissue or the orbital tissue when complicated ethmoid fractures occurred which make it more difficult to find the optic canal.Besides,the process of removing the uncinate process and the anterior and posterior ethmoid sinuses will cause greater iatrogenic damage.Therefore,to enhance the safety of operation and reduce iatrogenic injuries,a new minimally invasive surgical approach is urgently needed for optic canal decompression.Surgical treatment can relieve the symptoms of optic canal compression,but it cannot ameliorate and protect against secondary damage.Studies have shown that stem cell transplantation has a useful application prospect in the treatment of nerve injury diseases.Large number of studies have shown that mesenchymal stem cells can improve the motor function of rats in the repair of spinal cord injury,and improve the local microenvironment conducive to the recovery of neurological function.Transplantation of umbilical cord mesenchymal stem cells can significantly improve the neurological score of sequelae of traumatic head injury.Moreover,through local transplantation of MSCs can promote the repair of spinal cord injury,and the effect of MSCs on spinal cord regeneration is dose-dependent,the therapeutic effect can be enhanced by application as well.Intravitreal injection of bone marrow mesenchymal stem cells can promote the survival of ganglion cells and the growth of axons in rats with optic nerve injury and glaucoma.Inject dental pulp mesenchymal stem cells or induced pluripotent stem cells into the vitreous cavity can both promote the repair of optic nerve injury.Inject human umbilical cord mesenchymal stem cells into the vitreous cavity of rats with acute optic nerve injury has anti-RGC cell apoptosis,neuroprotective and anti-inflammatory effects in early stage.In addition to the ability of tissue regeneration and repair,bone marrow mesenchymal stem cells also have strong immune regulation and anti-inflammatory abilities.By regulating the switching of pro-inflammatory factors to anti-inflammatory factors at the injury site that the injection of mesenchymal stem cells can significantly improve the prognosis of nerve injury.Moreover,MSCs also have inflammation regulation and immune regulation capabilities.Therefore,we believe that transplanting MSCs into the optic nerve injury area may regulate inflammatory microenvironment of the optic nerve injury and promote the repair of the optic nerve injury and reduce glial scars formation.Objective1.To investigate the proliferation of h UC-MSCs on gelatin sponge scaffolds.2.To investigate the repair effect of h UC-MSCs gelatin sponge scaffold on optic nerve injury in rats.3.To study the security and efficacy of optic canal decompression under endoscopic transsphenoid optic canal decompression assisted by CT post-processing technique.4.A groundbreaking single-center,open-label,phase one clinical trial of local transplantation of MSCs in traumatic optic neuropathy,and systematically test the security of h UC-MSCs combined with optic nerve canal decompression for TON patients,so that explore a new effective method for the treatment of TON.Methods1.Isolate and culture primary MSCs from human umbilical cord and identify the amplified and purified MSCs through cell surface marker detection and multi-directional induction differentiation technology.A confocal microscope was used to observe the three-dimensional structure of the gelatin sponge,and the MTT method was used to detect the proliferation ability of MSCs on the gelatin sponge scaffold.2.The morphological and functional changes of MSCs on optic nerve injury were observed by pathological section and visual evoked potential.3.Using CT post-processing technique to imitate the location of the carotid artery and optic nerve on the inner wall of sphenoid sinus.By the post-processing technology,it is conducive to find the location of the optic canal during the operation and increase the operation safety.We also collected the clinical data such as vision,optic pipe diameter size,the length of the optic canal,and postoperative complications to evaluate the security and efficacy of the operation to introduce an auxiliary method to assist finding the position of optic canal.4.We enroll 20 patients with traumatic optic neuropathy and divided them into mesenchymal stem cell transplantation group(MSCT),which is a combination with optic canal decompression and the control group.Primary outcomes include the incidence of transplantrelated events and serious adverse events.The secondary outcome measure include change in best corrected vision change,change in color vision,and relative afferent pupillary deficiency(RAPD).Results1.In this study,MSCs were isolated by attachment method in vitro.The surface markers of the cells were positive for CD29,CD44,CD90 and CD105,but negative for CD34,CD31,and CD45.Gelatin sponge was used as a three-dimensional scaffold for MSCs.The scaffold has characters such as higher void fraction,non-swelling,and absorbable.The growth ability of MSCs on the gelatin sponge scaffold was expressively higher than that of the control group after 96 h of culture.2.In this study,we successfully established a rat optic nerve injury animal model.Morphological observations showed that the injury degree of optic nerve and retina in MSCs transplantation group was reduced compared with the injury group;In terms of function,at each time point after injury,the amplitude of FVEP in the injury group was excessively lower than that of the normal group,and the latency was prolonged with significant difference(P<0.05).The latent duration of FVEP in the experimental group compared with normal group was prolonged at each time point,and the difference was greatly different(P<0.05).The amplitude of FVEP of the experimental group was significantly different from the normal group at 1 to 3days after injury(P<0.05),but there was no statistically significant difference with the normal group at 7 to 14 days after injury(P>0.05).At each time point,the amplitude and latency between the experimental group and the injury control group were significantly different(P<0.05).3.Our results find that VA in 13 patients improved,with a total improve rate of 59.1%.No serious complications were found.We also found that the length of optic canal is different.And the inner wall of the optic canal was the longest(p < 0.05).The cranial mouth of the optic canal is the widest,which was significantly different from cranial mouth and orbital mouth(p< 0.05).4.All 20 patients completed the six-month follow-up.No one had any systemic or eye complications.Change in visual acuity(VA)at follow-up was not significantly different between group-1(1.77 ± 1.11)and group-2(2.36 ±0.81,P > 0.05),but group-1 showed a better visual outcome.Both groups showed significantly improve of vision comparing to baseline,respectively(P<0.05),but there was no statistical difference between the two groups(P>0.05).No serious complications were observed among patients.Conclusion1.Gelatin sponge is an ideal stem cell scaffold.It is high porous,non-swelling and can be absorbed by itself in a short time.2.Local transplantation of MSCs in the site of optic nerve injury can reduce the degree of optic nerve injury and promote the damage repair of rats.3.ETOCD was a feasible,safe,effective,and less-invasive approach for patients with TON.CT post-processing imaging helped recognize the optic canal during surgery.The decompression length of the medial wall may not need to be completely removed,especially near the cranial mouth.4.A single local transplantation of MSCs into the optic nerve is safe for patients suffering from traumatic optic nerve injury. |
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