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Vigabatrin can enhance electroretinographic responses in pigmented and albino rats

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Abstract

Purpose

To evaluate the effects of the antiepileptic medication vigabatrin (VGB) on the retina of pigmented rats.

Methods

Scotopic and photopic electroretinograms were recorded from dark- and light-adapted Long-Evans (pigmented) and Sprague Dawley (albino) rats administered, daily, 52–55 injections of 250 mg·kg−1·day−1 VGB or 25–26 injections of 500 mg·kg−1·day−1 VGB, or a corresponding number of sham injections. Sensitivity and saturated amplitude of the rod photoresponse (S, Rm P3) and postreceptor response (1/σ, Vm) were derived, as were sensitivity and amplitude of the cone-mediated postreceptor response (1/σ cone, Vm cone). The oscillatory potentials and responses to a series of flickering lights (6.25, 12.5, 25 and 50 Hz) were studied in the time and frequency domains. A subset of rats’ eyes was harvested for Western blotting or histology.

Results

Of the parameters derived from dark-adapted ERG responses, in both pigmented and albino rats, VGB repeatedly and reliably enhanced electroretinographic parameters; no significant ERG deficits were noted. No significant alterations were observed in ER/oxidative stress or in the Akt cell death/survival pathway. There were migrations of photoreceptor nuclei toward the RPE and outgrowths of bipolar cell dendrites into the outer nuclear layer in VGB-treated rats; these were never observed in sham-treated animals.

Conclusions

Although VGB is associated with retinal dysfunction in patients and VGB toxicity has been demonstrated by other laboratories in the albino rat, in our pigmented and albino rats, VGB did not induce deficits in, but rather enhanced, retinal function. Nonetheless, retinal neuronal dysplasia was observed.

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Acknowledgments

This work supported by a grant from Lundbeck LLC. We thank Prof. Serge Picaud for his suggestions regarding the importance of animal chow on the outcome of VGB treatment in murine animals and for providing details of his animals’ diet for comparison.

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Authors and Affiliations

  1. Department of Ophthalmology, Boston Children’s Hospital, 300 Longwood Ave, Fegan 4, Boston, MA, 02115, USA

    James D. Akula, Emily R. Noonan, Tara L. Favazza, Nan Zhang, Ronald M. Hansen & Anne B. Fulton

  2. Department of Neurology, Boston Children’s Hospital, Boston, MA, USA

    Alessia Di Nardo & Mustafa Sahin

  3. Harvard Medical School, Boston, MA, USA

    James D. Akula, Alessia Di Nardo, Nan Zhang, Mustafa Sahin, Ronald M. Hansen & Anne B. Fulton

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  1. James D. Akula
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Correspondence to Anne B. Fulton.

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Akula, J.D., Noonan, E.R., Di Nardo, A. et al. Vigabatrin can enhance electroretinographic responses in pigmented and albino rats. Doc Ophthalmol 131, 1–11 (2015). https://doi.org/10.1007/s10633-015-9491-0

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  • DOI: https://doi.org/10.1007/s10633-015-9491-0

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