Disruption of the Olfactoretinal Centrifugal Pathway May Relate to the Visual System Defect innight blindness bMutant Zebrafish

Abstract

We describe here a dominant mutation,night blindness b(nbb), which causes an age-related visual system defect in zebrafish. At 4–5 months of age, dark-adaptednbb^+/−mutants show abnormal visual threshold fluctuations when measured behaviorally. Light sensitizes the animals; thus early dark adaptation ofnbb^+/−fish is normal. After 2 hr of dark adaptation, however, visual thresholds ofnbb^+/−mutants are raised on average 2–3 log units, and rod system function is not detectable. Electroretinograms recorded fromnbb^+/−mutants are normal, but ganglion cell thresholds are raised in prolonged darkness, suggesting an inner retinal defect. The visual defect ofnbb^+/−mutants may be likely caused by an abnormal olfactoretinal centrifugal innervation; innbb^+/−mutants, the olfactoretinal centrifugal projection to the retina is disrupted, and the number of retinal dopaminergic interplexiform cells is reduced. A similar visual defect as shown bynbb^+/−mutants is observed in zebrafish in which the olfactory epithelium and olfactory bulb have been excised. Homozygousnbbfish display an early onset neural degeneration throughout the CNS and die by 7–8 d of age.