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Helena Lee, Jennifer Scott, Helen Griffiths, James Edward Self, Andrew Lotery; Proof of concept for oral Levodopa treatment in rescuing retinal morphology and visual function in a murine model of human albinism. Invest. Ophthalmol. Vis. Sci. 2019;60(9):530.
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© ARVO (1962-2015); The Authors (2016-present)
There is a paucity of treatment options for oculocutaneous albinism (OCA), a condition characterised by pigment deficiency and abnormal retinal development, which results in a significant degree of visual disability. L-DOPA, a signalling molecule which is essential for normal retinal development, is known to be deficient in OCA. Residual plasticity of the developing retina in young children with albinism has been demonstrated, suggesting a post-natal window for therapeutic rescue. The aim of this study is to investigate if post-natal retinal morphology and visual function in OCA can be improved through oral Levodopa supplementation, if administered during the critical period of neuroplasticity.
The effects of a 28-day course of oral Levodopa (1 mg/ml L-Dopa (Sigma) dissolved in drinking water) administered to 11 C57BL/6J-c2J OCA (CALB) mice from birth and 10 CALB mice from 28 days of age on retinal morphology and function were investigated using optical coherence tomography (OCT) (Bioptigen, 2.2µm axial resolution) and electroretinography (ERG) (Phoenix Micron III), respectively, and compared to 11 untreated CALB mice. A total of 336 examinations were obtained at 4, 5, 6, 8, 12 and 16 weeks of age. Generalised linear mixed regression modelling was used to analyse group differences.
We observed significant increases in retinal nerve fibre layer (z = 2.01, p = 0.044), outer nuclear layer (z = 1.97, p = 0.049) and photoreceptor end tips (z = 3.43, p = 0.001) OCT thickness measurements, significant increases in ERG A-wave (χ2 (9, N = 420) = 91.97, p < 0.0001)) and B-wave (χ2 (9, N = 420) = 121.24, p < 0.0001) amplitudes and significant reductions in A-wave latencies (χ2 (9, N = 420) = 47.92, p = 0.01) recorded from CALB mice treated with L-DOPA from birth, compared to untreated CALB mice. Interestingly, we did not observe any significant effects on ERG amplitudes or latencies in CALB mice treated with L-DOPA from 28 days of age.
We have demonstrated for the first time that abnormal retinal development, morphology and visual function can be rescued post-natally using oral L-DOPA supplementation, but only if administered during the critical period of neuroplasticity, in a murine model of human albinism.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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