Purchase this article with an account.
Lindsey Morey, Diana M Mitchell, Peter C Meighan, Michael D Varnum, Deborah L Stenkamp; Functional Physiology of the Regenerated Zebrafish Retina. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1679.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Zebrafish regenerate their retinas following damage, resulting in restoration of visual function (McGinn et al., 2018 J Neurosci). Behavioral measures of visual function are restored more rapidly following a lesion that destroys only neurons of the inner retina and spares photoreceptors (PR) and glia (=selective lesion), than following a lesion that destroys all retinal neurons and spares only glia (=extensive lesion) (Sherpa et al., 2014 Dev Neurobiol). Here we further evaluate the recovery of visual function through characterization of the electroretinogram (ERG) over time following these two types of retinal damage.
Right eyes of zebrafish (6mo–1.5yrs, both sexes) were lesioned with intravitreal injection of either 10 µM (extensive) or 2 µM (selective) ouabain. Left eyes served as unlesioned controls. Retinal neuronal communication was analyzed at selected recovery times using ERG recordings in intact zebrafish (extensive, n=4-13 per timepoint; selective, n=3-12 per timepoint). Eyes were then harvested and cryosectioned, permitting subsequent histological analysis of bipolar cells (BP), which is currently underway.
A qualitative study of the ERG waveforms focused on the “post-photoreceptor response” (PPR), which in a healthy retina is dominated by the “b-wave” or ON BP response, to assess BP function and connectivity to PRs during regeneration. There was a rapid reduction in the amplitude of the PPR after both extensive and selective lesions, though the reduction was greater for extensively-lesioned fish. During early stages of functional recovery after both types of lesions, we observed a deviated waveform, which was consistent with emergence of a d-wave (OFF BP response) elicited at light termination. After 45 days post-injury (DPI) for extensive and 21 DPI for selective lesions, the PPR waveform amplitude increased and peaked sooner after the light stimulus compared to earlier DPIs, suggesting emergence of the b-wave (ON BP response). By 90 DPI for extensive and 30 DPI for selective lesion, the PPR waveform became more typical of a healthy retina, but did not return to pre-lesion amplitudes.
Consistent with published behavioral results, PPR recovery following an extensive lesion occurred more slowly than PPR recovery following a selective lesion. Interestingly, the ERG waveform topography suggests that PR-OFF BP connectivity may functionally recover before PR-ON BP connectivity.
This is a 2021 ARVO Annual Meeting abstract.
This PDF is available to Subscribers Only