PURPOSE: To investigate rod function and survival after cone dysfunction and degeneration in a mouse model of cone cyclic nucleotide-gated (CNG) channel deficiency. METHODS: Rod function and survival in mice with cone CNG channel subunit CNGA3 deficiency (CNGA3-/- mice) were evaluated by electroretinographic (ERG), morphometric, and Western blot analyses. The arrangement, integrity, and ultrastructure of photoreceptor terminals were investigated by immunohistochemistry and electron microscopy. RESULTS: The authors found loss of cone function and cone death accompanied by impairment of rods and rod-driven signaling in CNGA3-/- mice. Scotopic ERG b-wave amplitudes were reduced by 15% at 1 month, 30% at 6 months, and 40% at 9 months and older, while scotopic a-wave amplitudes were decreased by 20% at 9 months, compared with ERGs of age-matched wild-type mice. Outer nuclear layer thickness in CNGA3-/- retina was reduced by 15% at 12 months compared with age-matched wild-type controls. This was accompanied by a 30%-40% reduction in expression of rod-specific proteins, including rhodopsin, rod transducin α-subunit, and glutamic acid-rich protein (GARP). Cone terminals in the CNGA3-/- retina showed a progressive loss of neurochemical and ultrastructural integrity. Abnormalities were observed as early as 1 month. Disorganized rod terminal ultrastructure was noted by 12 months. CONCLUSIONS: These findings demonstrate secondary rod impairment and degeneration after cone degeneration in mice with cone CNG channel deficiency. Loss of cone phototransduction accompanies the compromised integrity of cone terminals. With time, rod synaptic structure, function, and viability also become compromised.
PURPOSE: To investigate rod function and survival after cone dysfunction and degeneration in a mouse model of cone cyclic nucleotide-gated (CNG) channel deficiency. METHODS: Rod function and survival in mice with cone CNG channel subunit CNGA3 deficiency (CNGA3-/- mice) were evaluated by electroretinographic (ERG), morphometric, and Western blot analyses. The arrangement, integrity, and ultrastructure of photoreceptor terminals were investigated by immunohistochemistry and electron microscopy. RESULTS: The authors found loss of cone function and cone death accompanied by impairment of rods and rod-driven signaling in CNGA3-/- mice. Scotopic ERG b-wave amplitudes were reduced by 15% at 1 month, 30% at 6 months, and 40% at 9 months and older, while scotopic a-wave amplitudes were decreased by 20% at 9 months, compared with ERGs of age-matched wild-type mice. Outer nuclear layer thickness in CNGA3-/- retina was reduced by 15% at 12 months compared with age-matched wild-type controls. This was accompanied by a 30%-40% reduction in expression of rod-specific proteins, including rhodopsin, rod transducin α-subunit, and glutamic acid-rich protein (GARP). Cone terminals in the CNGA3-/- retina showed a progressive loss of neurochemical and ultrastructural integrity. Abnormalities were observed as early as 1 month. Disorganized rod terminal ultrastructure was noted by 12 months. CONCLUSIONS: These findings demonstrate secondary rod impairment and degeneration after cone degeneration in mice with cone CNG channel deficiency. Loss of cone phototransduction accompanies the compromised integrity of cone terminals. With time, rod synaptic structure, function, and viability also become compromised.
Authors: A J Mears; M Kondo; P K Swain; Y Takada; R A Bush; T L Saunders; P A Sieving; A Swaroop Journal: Nat Genet Date: 2001-12 Impact factor: 38.330
Authors: S Kohl; B Baumann; M Broghammer; H Jägle; P Sieving; U Kellner; R Spegal; M Anastasi; E Zrenner; L T Sharpe; B Wissinger Journal: Hum Mol Genet Date: 2000-09-01 Impact factor: 6.150
Authors: B Wissinger; D Gamer; H Jägle; R Giorda; T Marx; S Mayer; S Tippmann; M Broghammer; B Jurklies; T Rosenberg; S G Jacobson; E C Sener; S Tatlipinar; C B Hoyng; C Castellan; P Bitoun; S Andreasson; G Rudolph; U Kellner; B Lorenz; G Wolff; C Verellen-Dumoulin; M Schwartz; F P Cremers; E Apfelstedt-Sylla; E Zrenner; R Salati; L T Sharpe; S Kohl Journal: Am J Hum Genet Date: 2001-08-30 Impact factor: 11.025
Authors: Zhenqing Zhou; Frans Vinberg; Frank Schottler; Teresa A Doggett; Vladimir J Kefalov; Thomas A Ferguson Journal: Autophagy Date: 2015 Impact factor: 16.016
Authors: Aditya Venkatesh; Shan Ma; Yun Z Le; Michael N Hall; Markus A Rüegg; Claudio Punzo Journal: J Clin Invest Date: 2015-03-23 Impact factor: 14.808
Authors: Isaac Wang; Naheed W Khan; Kari Branham; B Wissinger; Susanne Kohl; J R Heckenlively Journal: Doc Ophthalmol Date: 2012-08-19 Impact factor: 2.379
Authors: Rehan S Shaikh; Peggy Reuter; Robert A Sisk; Tasleem Kausar; Mohsin Shahzad; Muhammad I Maqsood; Ateeq Yousif; Muhammad Ali; Saima Riazuddin; Bernd Wissinger; Zubair M Ahmed Journal: Eur J Hum Genet Date: 2014-07-23 Impact factor: 4.246
Authors: Bo Chen; Bogale Aredo; Yi Ding; Xin Zhong; Yuanfei Zhu; Cynthia X Zhao; Ashwani Kumar; Chao Xing; Laurent Gautron; Stephen Lyon; Jamie Russell; Xiaohong Li; Miao Tang; Priscilla Anderton; Sara Ludwig; Eva Marie Y Moresco; Bruce Beutler; Rafael L Ufret-Vincenty Journal: Proc Natl Acad Sci U S A Date: 2020-05-26 Impact factor: 11.205