Retinal Structural And Visual Functional Injury Caused By Two Ischemic Models And The Intervention

Both acute elevated intraocular pressure(IOP)and oxygen-induced retinopathy(OIR)are retinal ischemia models at different stages of retina development.The two retinal ischemia models are caused by different reasons and lead to abnormalities of retinal cytoarchitecture and visual function.Optic nerve transection is an extreme model of optic nerve injury.The adult animal retinas undergo the ischemia-perfusion in acute elevated IOP.The number of retinal ganglion cells continues to decline.In this study,using a rat model of retinal ischemia-reperfusion,and a one-time intravitreal brain-derived neurotrophic factor(BDNF)injection,we examined axon transportation function,continuity,physical presence in the optic nerve,and the expression level of proteins involved in axonal transportation.The process in this acute model resembles a fast-forward of changes in the chronical model.Therefore,impairment in axon transportation appears to be a common early process underlying different optic neuropathies.BDNF treatment relieved all reductions and significantly restored function.It is hopeful that effective intervention can be developed for all optic neuropathies targeting axon transportation.We analyzed the number of optic nerve axons,the area of optic nerve and the expression level of proteins involved in axonal transportation and glial fibrillary acidic protein(GFAP)after 8 weeks of optic nerve transection.We found the number of axons decreased to 10%,while the area of optic nerve reduced to 70% after 8 weeks of optic nerve transection.A large amount of GFAP expression indicated the gliosis activated by astrocytes filled the lost area.The results of Western Blotting implied the expression level of axonal transportation proteins were different between predominant glia and preponderant axons in optic nerve.The results reminded to pay attention to considering the glia activated when investigating the protein expression of optic nerve injury.OIR(an animal model of retinopathy of prematurity)is a disease with hyperoxia deterring retinal vessel development or degeneration early after birth.Room air is hypoxic due to severely retarded vasculature,which results in a massive abnormal proliferation of vessels,many of which extend into the vitreous body.The abnormal vessels extending into the vitreous may form filaments and cause retinal detachment and eventually blindness.In this study,we used clinically available medicine to reduce the IOP when the retina became hypoxic,improve the retinal perfusion and relieve the retinal ischemia.Rat OIR model was used in this study.We evaluated the abnormalities of retinal vessel density,cytoarchitecture and visual function in both OIR and treated groups.In OIR group,the retinal density decreased.In the central retina of the model group,the horizontal cells were completely wiped out,the outer plexiform layer was undetectable,and the rod bipolar cell dendrites sprouted into the outer nuclear layer.The visual function decreased significantly,i.e.visual acuity and contrast sensitivity.The treatment partially reverted these changes above.While the abnormality i.e.the thinner IPL did not recover after decreased the IOP.These impairments maybe the structural correlates of the residual impairments in visual functions.Since the medicine is clinically administered,this approach could be a noninvasive,easily applicable and economically affordable therapy for ROP.