Retinal rod photoreceptor-specific gene mutation perturbs cone pathway development.
Rod-specific photoreceptor dystrophies are complicated by the delayed death of genetically normal neighboring cones. In transgenic (Tg) swine with a rod-specific (rhodopsin) gene mutation, cone photoreceptor physiology was normal for months but later declined, consistent with delayed cone cell death. Surprisingly, cone postreceptoral function was markedly abnormal when cone photoreceptor physiology was still normal. The defect was localized to hyperpolarizing cells postsynaptic to the middle wavelength-sensitive cones. Recordings throughout postnatal development indicated a failure of cone circuitry maturation, a novel mechanism of secondary cone abnormality in rod dystrophy. The results have implications for therapy for human retinal dystrophies and raise the possibility that rod afferent activity plays a role in the postnatal maturation of cone retinal circuitry.
Banin
E
E
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia 19104, USA.
Cideciyan
A V
AV
Alemán
T S
TS
Petters
R M
RM
Wong
F
F
Milam
A H
AH
Jacobson
S G
SG
D019943:Amino Acid Substitution; D000818:Animals; D030801:Animals, Genetically Modified; D003623:Dark Adaptation / Q000502:physiology; D004596:Electroretinography; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D009434:Neural Pathways; D017949:Retinal Cone Photoreceptor Cells / Q000254:growth & development* / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000254:growth & development* / Q000502:physiology*; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000503:physiopathology; D012243:Rhodopsin / Q000235:genetics*; D013552:Swine; D013569:Synapses / Q000502:physiology
D012243:Rhodopsin