Kathleen M. Fitzgerald

Retinal signal transmission in Duchenne muscular dystrophy: evidence for dysfunction in the photoreceptor/depolarizing bipolar cell pathway.

There have been reports of abnormal retinal neurotransmission determined by electroretinography in boys with Duchenne and Becker muscular dystrophy. Dystrophin may play a role in transmitting signals between photoreceptors and the excitatory synapse of the ON-bipolar cell. These electroretinographic changes appeared to be limited to the rod ON-pathway but we felt there was also similar abnormality in the cone ON-pathway. We used long-duration stimuli to separate ON-(depolarizing bipolar cell) and OFF (hyperpolarizing bipolar cell) contributions to the cone-dominated ERG to better understand how the retina functions in boys with Duchenne muscular dystrophy. We recorded the electroretinograms of 11 boys with Duchenne muscular dystrophy and found abnormal signal transmission at the level of the photoreceptor and ON-bipolar cell in both the rod and cone generated responses. The OFF-bipolar cell that responds to the offset of the stimulus continues to function normally. The results support our hypothesis that retinal dystrophin plays a role in receptor function or controlling ion channels at the level of the photoreceptor and depolarizing bipolar cell.

Electroretinography in Congenital Idiopathic Nystagmus

Ganzfeld electroretinograms were recorded from 105 consecutive patients clinically believed to have congenital idiopathic nystagmus. Retinal disease causing congenital nystagmus was diagnosed in 59 patients (56%). Electroretinographic evaluation of children with nystagmus and apparently normal eyes has both diagnostic and prognostic value. In patients with congenital nystagmus with a normal ocular examination, a diagnosis of congenital idiopathic nystagmus cannot be inferred without electroretinographic evidence of normal retinal function.

ERG phenotype of a dystrophin mutation in heterozygous female carriers of Duchenne muscular dystrophy

PURPOSE Mutations in the dystrophin gene result in Duchenne muscular dystrophy (DMD). DMD is associated with an abnormal electroretinogram (ERG) if the mutation disrupts the translation of retinal dystrophin (Dp260). Our aim was to determine if incomplete ERG abnormalities would be associated with heterozygous carriers of dystrophin gene mutations. METHODS Ganzfeld ERGs were obtained under scotopic and photopic testing conditions from a family which includes the heterozygous maternal grandmother, the heterozygous mother, and her children, two affected boys and dizygotic twin sibs, an unaffected male and heterozygous female. Southern blot analyses were done to characterise the dystrophin mutation. RESULTS The dystrophin gene was found to contain a deletion encompassing exon 50. The ERGs in the two affected boys were abnormal, consistent with the DMD ERG phenotype. Serial ERGs of the heterozygous females were abnormal; however, they were less severely affected than the DMD boys. The ERG of the female sib showed a greater abnormality than her mother and maternal grandmother. The unaffected twin had a normal ERG. CONCLUSIONS The ERG shows abnormalities associated with carrier status in this family with a single exon deletion. A large study of confirmed obligate carriers is planned to clarify further the value of the ERG in detecting female heterozygous carriers of dystrophin gene mutations.

Optic nerve hypoplasia in association with brain anomalies and an abnormal electroretinogram

Abnormal electroretinograms (decreased amplitude and prolonged implicit time > 2 standard deviations) in several patients with optic nerve hypoplasia (ONH) and developmental brain anomalies led us to study the electroretinogram (ERG) in 34 consecutive cases of ONH presenting to our practice. Ages of the subjects were between 7 months and 13 years (mean, 4 years). ERGs were recorded from each eye by means of a contact lens electrode and ganzfeld stimuli. Rod-dominated dark-adapted responses were recorded as well as cone-dominated light-adapted responses. When clinically indicated, brain imaging by either computed tomography (CT) or magnetic resonance imaging (MRI) was performed. The ERG was abnormal in 12 (35%) of the children, including five (42%) with unilateral ONH. Imaging studies of the brain in 12 children with ONH and an abnormal ERG disclosed brain malformations in nine (75%) of them compared to five (23%) in the group with ONH and a normal ERG. An abnormal ERG associated with ONH and brain malformations may represent retinal or transsynaptic degeneration beyond the ganglion cell layer and implies a shared causative mechanism.