The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of ne...The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of neurons and to facilitate axonal regeneration in the central nervous system after injury. The deletion of the mTOR negative regulator phosphatase and tensin homolog （PTEN） enhances regeneration of adult corticospinal neurons and ganglion cells. In the present study, we used a tyrosine-mutated （Y444F） AAV2 vector to efficiently express a short hairpin RNA （shRNA） for silencing PTEN expression in retinal ganglion cells. We evaluated cell survival and axonal regeneration in a rat model of optic nerve axotomy. The rats received an intravitreal injection of wildtype AAV2 or Y444F mutant AAV2 （both carrying shRNA to PTEN） 4 weeks before optic nerve axotomy. Compared with the wildtype AAV2 vector, the Y444F mutant AAV2 vector enhanced retinal ganglia cell survival and stimulated axonal regeneration to a greater extent 6 weeks after axotomy. Moreover,post-axotomy injection of the Y444F AAV2 vector expressing the shRNA to PTEN rescued ～19% of retinal ganglion cells and induced axons to regenerate near to the optic chiasm. Taken together, our results demonstrate that PTEN knockdown with the Y444F AAV2 vector promotes retinal ganglion cell survival and stimulates long-distance axonal regeneration after optic nerve axotomy. Therefore, the Y444F AAV2 vector might be a promising gene therapy tool for treating optic nerve injury.展开更多
BACKGROUND Diffuse retinal pigment epitheliopathy(DRPE)associated with bullous retinal detachment is a severe variant of DRPE that is frequently misdiagnosed and often improperly treated.CASE SUMMARY A 36-year-old fem...BACKGROUND Diffuse retinal pigment epitheliopathy(DRPE)associated with bullous retinal detachment is a severe variant of DRPE that is frequently misdiagnosed and often improperly treated.CASE SUMMARY A 36-year-old female patient complained of"painless vision decline in the left eye with obscuration for 10 d".Slit-lamp microscopic fundus examination revealed white-yellow subretinal exudates in the posterior pole in both eyes,retinal detachment with shifting subretinal fluid in the left eye,and no retinal hiatus.Fundus fluorescein angiography revealed multiple subretinal leakage foci and localized hypofluorescent lesions with patched hyperfluorescence.There was fluorescence leakage in the retinal vessels in the retinal detachment area and occluded blood vessels in the lower and peripheral areas.Indocyanine green angiography revealed multifocal lamellar hyperfluorescence in the middle stage and low fluorescence in the retinal detachment area in the late stage.Retinal anatomical reduction significantly improved with intravitreal conbercept injections.CONCLUSION Intravitreal injection of conbercept can anatomically reattach the retina in patients with bullous retinal detachment.展开更多
基金supported by the Research Foundation of Jiangsu Provincial Commission of Health and Family Planning of China,No.H201653the Research Foundation of Changshu Science and Technology Bureau of China,No.CS201616
文摘The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of neurons and to facilitate axonal regeneration in the central nervous system after injury. The deletion of the mTOR negative regulator phosphatase and tensin homolog （PTEN） enhances regeneration of adult corticospinal neurons and ganglion cells. In the present study, we used a tyrosine-mutated （Y444F） AAV2 vector to efficiently express a short hairpin RNA （shRNA） for silencing PTEN expression in retinal ganglion cells. We evaluated cell survival and axonal regeneration in a rat model of optic nerve axotomy. The rats received an intravitreal injection of wildtype AAV2 or Y444F mutant AAV2 （both carrying shRNA to PTEN） 4 weeks before optic nerve axotomy. Compared with the wildtype AAV2 vector, the Y444F mutant AAV2 vector enhanced retinal ganglia cell survival and stimulated axonal regeneration to a greater extent 6 weeks after axotomy. Moreover,post-axotomy injection of the Y444F AAV2 vector expressing the shRNA to PTEN rescued ～19% of retinal ganglion cells and induced axons to regenerate near to the optic chiasm. Taken together, our results demonstrate that PTEN knockdown with the Y444F AAV2 vector promotes retinal ganglion cell survival and stimulates long-distance axonal regeneration after optic nerve axotomy. Therefore, the Y444F AAV2 vector might be a promising gene therapy tool for treating optic nerve injury.
基金Supported by Guiding Project of Changshu Health Committee,No.CSWZD202021Project of the Affiliated Changshu Hospital of Xuzhou Medical University,No.CSEY202125。
文摘BACKGROUND Diffuse retinal pigment epitheliopathy(DRPE)associated with bullous retinal detachment is a severe variant of DRPE that is frequently misdiagnosed and often improperly treated.CASE SUMMARY A 36-year-old female patient complained of"painless vision decline in the left eye with obscuration for 10 d".Slit-lamp microscopic fundus examination revealed white-yellow subretinal exudates in the posterior pole in both eyes,retinal detachment with shifting subretinal fluid in the left eye,and no retinal hiatus.Fundus fluorescein angiography revealed multiple subretinal leakage foci and localized hypofluorescent lesions with patched hyperfluorescence.There was fluorescence leakage in the retinal vessels in the retinal detachment area and occluded blood vessels in the lower and peripheral areas.Indocyanine green angiography revealed multifocal lamellar hyperfluorescence in the middle stage and low fluorescence in the retinal detachment area in the late stage.Retinal anatomical reduction significantly improved with intravitreal conbercept injections.CONCLUSION Intravitreal injection of conbercept can anatomically reattach the retina in patients with bullous retinal detachment.
