Visual function in regenerating teleost retina following cytotoxic lesioning

Abstract

Teleost fish retinas can regenerate in vivo in adulthood. Retinal and visual function was assessed in adult goldfish following comprehensive retinal destruction by intraocular injection of ouabain. Electroretinograms (ERGs) and the dorsal light reflex (DLR) were used to evaluate the return of visual function. ERGs were detectable in regenerating eyes 50 to 70 days following ouabain injection. Amplitudes of both a- and b-waves increased steadily through day 210 following ouabain treatment, at which time a-wave amplitude was 90% and b-wave amplitude approached 50% of the contralateral control eye. The progressive gain observed in the a-wave was attributed to photoreceptor regeneration. The increase in b-wave amplitude was attributed to an increase in the number of inner nuclear layer cells and the number and efficacy of neuronal connections to or within the inner retina. The photopic spectral sensitivity of the b-wave in regenerating retina closely matched the intrafish control retina, suggesting that the relative numbers of cone photoreceptors was normal in regeneration. The recovery of the DLR (indicated by improved postural balance during regeneration) paralleled electrophysiological gains during retinal regeneration. Fish displayed a marked longitudinal body imbalance toward the control eye following retinal destruction. Improvement in equilibrium was correlated with increasing b-wave amplitudes. When the b-wave reached 50% of control amplitude (30 weeks), normal posture was restored. The return of the ERG indicates that photoreceptors and their synaptic connections must be functional in regenerating retina. Failure of the retina to regenerate produced an abnormal DLR that persisted through 30 weeks and ERGs were not measurable. The return of normal equilibrium indicates that the regenerating retina can establish central connections to the brain, and that the regenerated connections can mediate functional visual behavior.