Researchers at the Department of Neurobiology and Behavior, University of California, Irvine, have reported a study on pre-clinical research suggesting a significant restoration of vision with retinoid therapy measuring increases in the number and response amplitude of visually responsive neurons in the primary visual cortex (V1). The researchers suggested that results “illustrate the significant plasticity of the adult central visual system and underscore the therapeutic potential of retinoid administration for adults with retinal diseases”. The report was published in Current Biology (Huh et al 2022, Vol. 32, 1-9), presenting valuable neurobiological data under-pining previous applications in the clinic with synthetic retinoids.
The synthetic compound (9-cis-retinyl acetate, or 9-cis-R-Ac) was prepared to replace the normal functioning of 11-cis retinal. The compound is understood to convert in the body to 9-cis retinal to combine with opsin forming iso-rhodopsin and initiating the phototransduction cascade upon activation by light. The compound is a prodrug converted by hydrolysis in vivo to 9-cis-retinol, then converted to 9-cis-retinal, and thereby restoring the key biochemical component of the retinoid cycle. The current research used an experimental model of LCA, the lecithin:retinol acyltransferase knockout (Lrat -/-), in order to assess recovery of the central visual circuit. Intraperitoneal administration of the synthetic retinoid (40 mg/kg) was applied for seven consecutive days showing substantial 9-cis-retinal accumulation in the eye “and produced a rapid and prolonged improvement in light-induced ERG activity and optomotor reflexes (OMR)”, compared to controls. Treatment led to “a significant increase in the amplitude of V1 activation (median of 28% increase when using stimuli with max. luminance of 33 cd/m2”. In contrast, control exhibited a progressive decrease in response amplitude over time.
Following the results, Dr. Sunil Gandhi, a fellow of UCI’s Center for the Neurobiology of Learning and Memory and a member of the Center for Translational Vision Research commented that, “[i]mmediately after the treatment, the signals coming from the opposite-side eye, which is the dominant pathway in the mouse, activated two times more neurons in the brain. What was even more mind-blowing was that the signals coming from the same-side eye pathway activated five-fold more neurons in the brain after the treatment and this impressive effect was long-lasting. The restoration of visual function at the level of the brain was much greater than expected from the improvements we saw at the level of the retinae. The fact that this treatment works so well in the central visual pathway in adulthood supports a new concept, which is that there is latent potential for vision that is just waiting to be triggered.”