AIM: To study the trends of major causes of visual impairment(VI) in adults in Sichuan,China and evaluate the effect of aging on the trends. ·METHODS: We used data from the National Sample Survey on Disabilities(...AIM: To study the trends of major causes of visual impairment(VI) in adults in Sichuan,China and evaluate the effect of aging on the trends. ·METHODS: We used data from the National Sample Survey on Disabilities(NSSD) in Sichuan province conducted in 1987 and 2006. The age-adjusted prevalence of major causes of VI and the prevalence stratified by age in each cause were calculated and compared. The association between age and each cause of VI was also analyzed.·RESULTS: Retinal disease increased and became the second leading cause of VI in 2006 while blinding trachoma decreased markedly. Cataract and non-trachomatous corneal diseases were among the leading causes of VI in both years. We found associations between age and causes of VI,with age showing the strongest association with cataract and relatively lower associations with other causes. · CONCLUSION: In the last two decades,dramatic changes occurred in the major causes of VI with significantly increased retinal disease and decreased blinding trachoma. Aging of the population might be an important factor accounting for the changed trends of VI. Understanding the prevalence of VI,its major causes and trends over time can assist in prioritizing and developing effective interventional strategies and monitoring their impact.展开更多
Objective: To evaluate the safety and efficacy of the relatively selective M1 antagonist pirenzepine hydrochloride in slowing the progression of myopia in school- aged children. Methods: This was a parallel- group, pl...Objective: To evaluate the safety and efficacy of the relatively selective M1 antagonist pirenzepine hydrochloride in slowing the progression of myopia in school- aged children. Methods: This was a parallel- group, placebo- controlled, double- masked study in healthy children, aged 8 to 12 years, with a spherical equivalent of- 0.75 to- 4.00 diopters (D) and astigmatism of 1.00 D or less. Patients underwent a baseline complete eye examination and regular examinations during a 1- year period. The setting was 13 US academic clinics and private practices. Patients were randomized in a 2:1 ratio to receive 2% pirenzepine ophthalmic gel or a placebo control twice daily for 1 year. Results: At study entry, the spherical equivalent was mean± SD- 2.098± 0.903 D for the pirenzepine group (n=117) and- 1.933± 0.825 D for the placebo group (n=57, P=.22). At 1 year, there was a mean increase in myopia of 0.26 D in the pirenzepine group vs 0.53 D in the placebo group (P < .001). No patients in the placebo group and 13 (11% ) of 117 patients in the pirenzepine group discontinued participation in the study because of adverse effects (5 [4% Abstractof 117 due to excessive antimuscarinic effects)- . Conclusions: Pirenzepine is effective and relatively safe in slowing the progression of myopia during a 1- year treatment period.展开更多
We recently found that growth factor receptor-bound(Grb)protein 14 is a novel physiological modulator of photoreceptor specific cyclic nucleotide-gated channel alpha subunit(CNGA1).Grb14 promotes the CNG channel closu...We recently found that growth factor receptor-bound(Grb)protein 14 is a novel physiological modulator of photoreceptor specific cyclic nucleotide-gated channel alpha subunit(CNGA1).Grb14 promotes the CNG channel closure through its Ras-associating(RA)domain.In the current study we show that this RA domain-mediated inhibition of rod CNG channel is electrostatic in nature.Grb14 competes with cGMP for the CNGA1 binding pocket and electrostatically interacts with Arg^(559) through a negatively chargedβ-turn at its RA domain.Moreover,the three Glu residues(180–182)in Grb14 are absolutely critical for electrostatic interaction with the cGMP binding pocket and resultant inhibition.Our study also demonstrates that substitution of Lys^(140) for Ala or in combination with polyglutamte mutants of Grb14 results in a significantly reduced binding with CNGA1.These results suggest that in addition to Glu^(180–182) and Lys^(140),other residues in Grb14 may be involved in the electrostatic interaction with CNGA1.The RA domain is highly conserved among the members of Grb7 family of proteins,which includes Grb7,Grb10 and Grb14.Further,only Grb14 is able to modulate the channel activity,but not Grb7 and Grb10.All together,it suggests the existence of a divergence in RA domains among the members of the Grb7 family.展开更多
Dear Editor,Protein tyrosine phosphatase-1B(PT-P1B)is an abundant,widely expressed non-receptor tyrosine phosphatase,which is thought to be a key negative regulator of insulin signaling(Tonks,2003).Increased and prolo...Dear Editor,Protein tyrosine phosphatase-1B(PT-P1B)is an abundant,widely expressed non-receptor tyrosine phosphatase,which is thought to be a key negative regulator of insulin signaling(Tonks,2003).Increased and prolonged tyrosine phosphorylation of the insulin recep-tor(IR)was observed in mice lacking PTP1B(Elchebly et al.,1999).展开更多
Ras proteins are signal-transducing GTPases that cycle between inactive GDP-bound and active GTP-bound forms.Ras is a prolific signaling molecule interacting with a spectrum of effector molecules and acting through mo...Ras proteins are signal-transducing GTPases that cycle between inactive GDP-bound and active GTP-bound forms.Ras is a prolific signaling molecule interacting with a spectrum of effector molecules and acting through more than one signaling pathway.The Ras-effector proteins contain a Ras-associating(RA)domain through which these associate with Ras in a GTP-dependent manner.The RA domain is highly conserved among the members of the growth factor receptor-bound(Grb)7 family of proteins which includes Grb7,Grb10 and Grb14.Our laboratory has reported an unusual observation that RA domain of Grb14 binds to the C-terminal nucleotide binding site of cyclic nucleotide gated channel(CTRCNGA1)and inhibits the channel activity.Molecular modeling of the CTR-CNGA1 displays 50%---70%tertiary structural similarity towards Ras proteins.We named this region as Ras-like domain(RLD).The interaction between RA-Grb14 and RLD-CNGA1 is mediated through a simple protein-protein interaction temporally and spatially regulated by light and cGMP.It is interesting to note that Grb14 binds to GTPase-mutant Rab5,a Ras-related small GTPase whereas Grb10 binds only to GTP-bound form of active Rab5 but not to GTPase-defective mutant Rab5.These results suggest that Grb14 might have been evolved later in the evolution that binds to both Ras and nucleotide binding proteins such as CNGA1.Our studies also suggest that eukaryotic CNG channels could be evolved through a gene fusion between prokaryotic ion channels and cyclic nucleotide binding proteins,both of which might have undergone several sequence variations for functional adaptation during evolution.展开更多
基金Supported by National Natural Science Foundation of China(NO.81271035/H1205)The Cooperative Program of the Second National Sample Survey on Disabilities in Sichuan Province,China(No.303005002164)A departmental grant from Research to Prevent Blindness,New York,NY(PLH,BKF).Award Number P50DA010075-16 from the National Institute on Drug Abuse(NIDA)
文摘AIM: To study the trends of major causes of visual impairment(VI) in adults in Sichuan,China and evaluate the effect of aging on the trends. ·METHODS: We used data from the National Sample Survey on Disabilities(NSSD) in Sichuan province conducted in 1987 and 2006. The age-adjusted prevalence of major causes of VI and the prevalence stratified by age in each cause were calculated and compared. The association between age and each cause of VI was also analyzed.·RESULTS: Retinal disease increased and became the second leading cause of VI in 2006 while blinding trachoma decreased markedly. Cataract and non-trachomatous corneal diseases were among the leading causes of VI in both years. We found associations between age and causes of VI,with age showing the strongest association with cataract and relatively lower associations with other causes. · CONCLUSION: In the last two decades,dramatic changes occurred in the major causes of VI with significantly increased retinal disease and decreased blinding trachoma. Aging of the population might be an important factor accounting for the changed trends of VI. Understanding the prevalence of VI,its major causes and trends over time can assist in prioritizing and developing effective interventional strategies and monitoring their impact.
文摘Objective: To evaluate the safety and efficacy of the relatively selective M1 antagonist pirenzepine hydrochloride in slowing the progression of myopia in school- aged children. Methods: This was a parallel- group, placebo- controlled, double- masked study in healthy children, aged 8 to 12 years, with a spherical equivalent of- 0.75 to- 4.00 diopters (D) and astigmatism of 1.00 D or less. Patients underwent a baseline complete eye examination and regular examinations during a 1- year period. The setting was 13 US academic clinics and private practices. Patients were randomized in a 2:1 ratio to receive 2% pirenzepine ophthalmic gel or a placebo control twice daily for 1 year. Results: At study entry, the spherical equivalent was mean± SD- 2.098± 0.903 D for the pirenzepine group (n=117) and- 1.933± 0.825 D for the placebo group (n=57, P=.22). At 1 year, there was a mean increase in myopia of 0.26 D in the pirenzepine group vs 0.53 D in the placebo group (P < .001). No patients in the placebo group and 13 (11% ) of 117 patients in the pirenzepine group discontinued participation in the study because of adverse effects (5 [4% Abstractof 117 due to excessive antimuscarinic effects)- . Conclusions: Pirenzepine is effective and relatively safe in slowing the progression of myopia during a 1- year treatment period.
基金by grants from the NIH(EY016507EY00871EY12190).CNGA1 and CNGB1 subunit channel antibodies were a kind gift from Dr.Robert Molday,University of British Columbia(Canada).
文摘We recently found that growth factor receptor-bound(Grb)protein 14 is a novel physiological modulator of photoreceptor specific cyclic nucleotide-gated channel alpha subunit(CNGA1).Grb14 promotes the CNG channel closure through its Ras-associating(RA)domain.In the current study we show that this RA domain-mediated inhibition of rod CNG channel is electrostatic in nature.Grb14 competes with cGMP for the CNGA1 binding pocket and electrostatically interacts with Arg^(559) through a negatively chargedβ-turn at its RA domain.Moreover,the three Glu residues(180–182)in Grb14 are absolutely critical for electrostatic interaction with the cGMP binding pocket and resultant inhibition.Our study also demonstrates that substitution of Lys^(140) for Ala or in combination with polyglutamte mutants of Grb14 results in a significantly reduced binding with CNGA1.These results suggest that in addition to Glu^(180–182) and Lys^(140),other residues in Grb14 may be involved in the electrostatic interaction with CNGA1.The RA domain is highly conserved among the members of Grb7 family of proteins,which includes Grb7,Grb10 and Grb14.Further,only Grb14 is able to modulate the channel activity,but not Grb7 and Grb10.All together,it suggests the existence of a divergence in RA domains among the members of the Grb7 family.
基金This work was supported by grants from the NIH(Nos.EY016507,EY00871,and EY021725)by an unrestricted depart-mental grant from Research to Prevent Blind-ness,Inc.
文摘Dear Editor,Protein tyrosine phosphatase-1B(PT-P1B)is an abundant,widely expressed non-receptor tyrosine phosphatase,which is thought to be a key negative regulator of insulin signaling(Tonks,2003).Increased and prolonged tyrosine phosphorylation of the insulin recep-tor(IR)was observed in mice lacking PTP1B(Elchebly et al.,1999).
基金by grants from the NIH(EY016507,EY00871,EY12190).
文摘Ras proteins are signal-transducing GTPases that cycle between inactive GDP-bound and active GTP-bound forms.Ras is a prolific signaling molecule interacting with a spectrum of effector molecules and acting through more than one signaling pathway.The Ras-effector proteins contain a Ras-associating(RA)domain through which these associate with Ras in a GTP-dependent manner.The RA domain is highly conserved among the members of the growth factor receptor-bound(Grb)7 family of proteins which includes Grb7,Grb10 and Grb14.Our laboratory has reported an unusual observation that RA domain of Grb14 binds to the C-terminal nucleotide binding site of cyclic nucleotide gated channel(CTRCNGA1)and inhibits the channel activity.Molecular modeling of the CTR-CNGA1 displays 50%---70%tertiary structural similarity towards Ras proteins.We named this region as Ras-like domain(RLD).The interaction between RA-Grb14 and RLD-CNGA1 is mediated through a simple protein-protein interaction temporally and spatially regulated by light and cGMP.It is interesting to note that Grb14 binds to GTPase-mutant Rab5,a Ras-related small GTPase whereas Grb10 binds only to GTP-bound form of active Rab5 but not to GTPase-defective mutant Rab5.These results suggest that Grb14 might have been evolved later in the evolution that binds to both Ras and nucleotide binding proteins such as CNGA1.Our studies also suggest that eukaryotic CNG channels could be evolved through a gene fusion between prokaryotic ion channels and cyclic nucleotide binding proteins,both of which might have undergone several sequence variations for functional adaptation during evolution.
