Primary open-angle glaucoma(POAG)is the leading cause of irreversible blindness worldwide,primarily due to the degeneration of retinal ganglion cells(RGCs).In this study,we reported vav guanine nucleotide exchange fac...Primary open-angle glaucoma(POAG)is the leading cause of irreversible blindness worldwide,primarily due to the degeneration of retinal ganglion cells(RGCs).In this study,we reported vav guanine nucleotide exchange factor 2(VAV2)as a POAG-associated gene.Through whole exome sequencing(WES)of 398 Han Chinese POAG patients and 2,010 controls,we discovered nine rare VAV2 variants linked to POAG(P_burden=1.40×10^(-6)).Functional analyses revealed that these variants disrupted normal VAV2 protein function,leading to compromised cytoskeletal organization in human trabecular meshwork cells and impaired axonal growth in the 661W cell line.In vivo,Vav2 knockout mice exhibited key POAG features,including increased intraocular pressure(IOP),abnormal trabecular meshwork structure,reduced visual sensitivity,and RGC loss.This study also implicated VAV2 in the modulation of the Rho signaling pathway,which is essential for maintaining trabecular meshwork integrity and neuronal function.Taken together,this research identified VAV2 as a candidate gene for POAG and suggests VAV2 as a potential target for genetic screening of POAG diagnostics.展开更多
Purpose To investigate the intraocular pressure (IOP) variations occurring aft er indirect diode laser photocoagulation for threshold retinopathy of prematurit y. Design Prospective, nonrandomized, comparative study. ...Purpose To investigate the intraocular pressure (IOP) variations occurring aft er indirect diode laser photocoagulation for threshold retinopathy of prematurit y. Design Prospective, nonrandomized, comparative study. Participants A study gr oup 21 consecutive premature babies (42 eyes) undergoing diode laser photocoagul ation for retinopathy of prematurity and control groups 32 premature babies (64 eyes) undergoing retinal examination with or without scleral indentation. Interv ention Intraocular pressure was measured with a portable electronic tonometer be fore, immediately after, and 1, 2, and 3 days after diode laser photocoagulation in the study group; before retinal examination in control group 1; and before a nd after retinal examination with scleral indentation in control group 2. Main o utcome measure Intraocular pressure after diode laser photocoagulation for thres hold retinopathy of prematurity. Results Mean IOP in the study group rose from 1 5 mmHg (standard deviation SD=4.1) before coagulation to 33.2 mmHg (SD = 7.8; range, 20-50) immediately after, and then dropped to 22.2 (SD=5.2), 16.5 (SD=3) , and 14.5 mmHg (SD=2.1) 1, 2, and 3 days later, respectively. All the changes w ere statistically significant at P < 0.0001, except for the difference between d ays 2 and 3(P=0.096). Mean baseline IOPs were 16.3 mmHg (SD=3.7) in control grou p 1 and 15.7 mmHg (SD=2.3) in control group 2 (P=0.84 between control group 1 an d study group, and P=0.32 between control group 2 and the study group). At termi nation of the retinal examination with scleral indentation (control group 2), IO P measured 15.1 mmHg (SD=2.2) (P=0.49 compared with baseline). Conclusions Intra ocular pressure may be significantly elevated after diode laser photocoagulation for retinopathy of prematurity. The mechanism and long-term clinical implicati ons of this observation should be investigated.展开更多
基金supported by the National Natural Science Foundation of China(81970839,82271105,82330030,82121003,82101163)Sichuan Science and Technology Program(2023ZYD0059,2021YFS0369)+1 种基金Chengdu Science and Technology Program(2024-YF0501180-SN)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-032)。
文摘Primary open-angle glaucoma(POAG)is the leading cause of irreversible blindness worldwide,primarily due to the degeneration of retinal ganglion cells(RGCs).In this study,we reported vav guanine nucleotide exchange factor 2(VAV2)as a POAG-associated gene.Through whole exome sequencing(WES)of 398 Han Chinese POAG patients and 2,010 controls,we discovered nine rare VAV2 variants linked to POAG(P_burden=1.40×10^(-6)).Functional analyses revealed that these variants disrupted normal VAV2 protein function,leading to compromised cytoskeletal organization in human trabecular meshwork cells and impaired axonal growth in the 661W cell line.In vivo,Vav2 knockout mice exhibited key POAG features,including increased intraocular pressure(IOP),abnormal trabecular meshwork structure,reduced visual sensitivity,and RGC loss.This study also implicated VAV2 in the modulation of the Rho signaling pathway,which is essential for maintaining trabecular meshwork integrity and neuronal function.Taken together,this research identified VAV2 as a candidate gene for POAG and suggests VAV2 as a potential target for genetic screening of POAG diagnostics.
文摘Purpose To investigate the intraocular pressure (IOP) variations occurring aft er indirect diode laser photocoagulation for threshold retinopathy of prematurit y. Design Prospective, nonrandomized, comparative study. Participants A study gr oup 21 consecutive premature babies (42 eyes) undergoing diode laser photocoagul ation for retinopathy of prematurity and control groups 32 premature babies (64 eyes) undergoing retinal examination with or without scleral indentation. Interv ention Intraocular pressure was measured with a portable electronic tonometer be fore, immediately after, and 1, 2, and 3 days after diode laser photocoagulation in the study group; before retinal examination in control group 1; and before a nd after retinal examination with scleral indentation in control group 2. Main o utcome measure Intraocular pressure after diode laser photocoagulation for thres hold retinopathy of prematurity. Results Mean IOP in the study group rose from 1 5 mmHg (standard deviation SD=4.1) before coagulation to 33.2 mmHg (SD = 7.8; range, 20-50) immediately after, and then dropped to 22.2 (SD=5.2), 16.5 (SD=3) , and 14.5 mmHg (SD=2.1) 1, 2, and 3 days later, respectively. All the changes w ere statistically significant at P < 0.0001, except for the difference between d ays 2 and 3(P=0.096). Mean baseline IOPs were 16.3 mmHg (SD=3.7) in control grou p 1 and 15.7 mmHg (SD=2.3) in control group 2 (P=0.84 between control group 1 an d study group, and P=0.32 between control group 2 and the study group). At termi nation of the retinal examination with scleral indentation (control group 2), IO P measured 15.1 mmHg (SD=2.2) (P=0.49 compared with baseline). Conclusions Intra ocular pressure may be significantly elevated after diode laser photocoagulation for retinopathy of prematurity. The mechanism and long-term clinical implicati ons of this observation should be investigated.
