July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Oral human-equivalent L-DOPA/Carbidopa dosages administered during the postnatal critical period of neuroplasticity rescues retinal morphology and visual function in a mouse model of human albinism
Author Affiliations & Notes
  • Aida Sanchez-Bretano
    Clinical and Experimental Sciences, University of Southampton, Southampton, Hampshire, United Kingdom
  • Jennifer Ann Scott
    Clinical and Experimental Sciences, University of Southampton, Southampton, Hampshire, United Kingdom
  • Tutte Newall
    Clinical and Experimental Sciences, University of Southampton, Southampton, Hampshire, United Kingdom
  • Savannah Lynn
    Clinical and Experimental Sciences, University of Southampton, Southampton, Hampshire, United Kingdom
  • Helen Griffiths
    Clinical and Experimental Sciences, University of Southampton, Southampton, Hampshire, United Kingdom
  • Ahmed Salman
    Clinical and Experimental Sciences, University of Southampton, Southampton, Hampshire, United Kingdom
  • Andrew Lotery
    Clinical and Experimental Sciences, University of Southampton, Southampton, Hampshire, United Kingdom
  • J. Arjuna Ratnayaka
    Clinical and Experimental Sciences, University of Southampton, Southampton, Hampshire, United Kingdom
  • James Edward Self
    Clinical and Experimental Sciences, University of Southampton, Southampton, Hampshire, United Kingdom
  • Helena Lee
    Clinical and Experimental Sciences, University of Southampton, Southampton, Hampshire, United Kingdom
  • Footnotes
    Commercial Relationships   Aida Sanchez-Bretano, None; Jennifer Scott, None; Tutte Newall, None; Savannah Lynn, None; Helen Griffiths, None; Ahmed Salman, None; Andrew Lotery, None; J. Arjuna Ratnayaka, None; James Self, None; Helena Lee, None
  • Footnotes
    Support  Medical Research Council (MRC), London, UK (grant number: MR/R007640/1), Academy of Medical Sciences (AMS) (grant number: SGL014\1009), Gift of Sight, University of Southampton Research Management committee and the National Institute for Health Research (NIHR).
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1393. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Aida Sanchez-Bretano, Jennifer Ann Scott, Tutte Newall, Savannah Lynn, Helen Griffiths, Ahmed Salman, Andrew Lotery, J. Arjuna Ratnayaka, James Edward Self, Helena Lee; Oral human-equivalent L-DOPA/Carbidopa dosages administered during the postnatal critical period of neuroplasticity rescues retinal morphology and visual function in a mouse model of human albinism. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1393. doi: https://doi.org/.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Evidence of ongoing retinal development in children with albinism has been demonstrated. L-DOPA, a key molecule for the correct development of the retina, is known to be deficient in the developing albino eye, resulting in abnormalities of retinal structure and visual impairment. Thus, we investigated if human equivalent doses of L-DOPA/Carbidopa (i.e. doses established for the treatment of infantile dystonia and amblyopia), can rescue visual function in a mouse model of human oculocutaneous albinism (OCA), if administered during the postnatal critical period of neuroplasticity.

Methods : C57BL/6J (B6; n=24) and C57BL/6J-c2J OCA (CALBs; n=10) mice were treated with a 28-day course of oral L-DOPA/Carbidopa 9.4/2.3 mg/kg, from 15 to 43 days postnatal age (PNA) and compared to untreated B6 mice (n=8) and CALBs (n=16). Retinal morphology and function were assessed at 6 weeks PNA using optical coherence tomography and electroretinography. Photopic spatial frequency thresholds (i.e. visual acuity) were assessed by optokinetic nystagmus using an OptoMotry system at 7 weeks PNA.

Results : At 6 weeks PNA, the outer nuclear layer (ONL) thickness of untreated CALBs was significantly increased (61.5±0.2 vs 66.6±0.2 μm; p=0.0004). The ONL of treated CALBs (61.9±0.2 μm) recovered the same thickness found in B6 mice (61.3±0.3μm; p=0.779). A- and B-wave amplitudes were significantly diminished in untreated CALBs (284±18 vs 176±15 μV; p=0.0033; and -136±19 vs -85±9 μV; p=0.0298). Treated CALBs recovered amplitudes similar to B6 mice (340±16 and -183±9 μV, respectively). Photopic spatial frequency thresholds, were significantly lower in untreated CALBs; clock-wise (CW) (0.458±0.059 vs 0.188±0.095 c/d; p=0.0038) and clock-counter-wise (CCW) (0.401±0.012 vs 0.107±0.001 c/d; p=0.0012). Both thresholds improved in treated CALBs, reaching comparable levels to B6 mice (CW: 0.419±0.021 vs 0.292±0.026 c/d; p=0.1009; and CCW: 0.382±0.027 vs 0.330±0.044 c/d, respectively; p=0.5778).

Conclusions : Our results demonstrate that human equivalent doses of oral L-DOPA/Carbidopa supplementation during the critical postnatal period of retinal neuroplasticity can rescue visual function and retinal morphology in a mouse model of albinism. This novel work brings an effective treatment for children with albinism one step closer.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×