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 r od-specific (rhodopsin) gene mutation, cone photoreceptor physiology was no rmal for months but later declined, consistent with delayed cone cell death . Surprisingly, cone postreceptoral function was markedly abnormal when con e photoreceptor physiology was still normal. The defect was localized to hy perpolarizing cells postsynaptic to the middle wavelength-sensitive cones. Recordings throughout postnatal development indicated a failure of cone cir cuitry maturation, a novel mechanism of secondary cone abnormality in rod d ystrophy. The results have implications for therapy for human retinal dystr ophies and raise the possibility that rod afferent activity plays a role in the postnatal maturation of cone retinal circuitry.