Filtration Of Short-Wavelength Light Provides Therapeutic Benefit In Retinitis Pigmentosa Caused By A Common Rhodopsin Mutation

PURPOSE. The role of light exposure in accelerating retinitis pigmentosa (RP) remains controversial. Faster degeneration has however been observed in the inferior than superior retina in several forms ("sector'' RP), including those caused by the rhodopsin P23H mutation, suggesting a modifying role of incident light exposure in such cases. Rearing of equivalent animal models in complete darkness has been shown to slow the degeneration. Here we investigate the use of red filters as a potential treatment strategy, with the hypothesis that minimizing retinal exposure to light <600 nm to which rods are maximally sensitive may provide therapeutic benefit.METHODS. Knockin mice heterozygous for the P23H dominant rhodopsin mutation (Rho(P23H/+)) housed in red-tinted plastic cages were divided at weaning into either untinted or red-tinted cages. Subsequently, photoreceptor layer (PRL) thickness was measured by spectral-domain ocular coherence tomography, retinal function quantified by ERG, and cone morphology determined by immunohistochemical analysis (IHC) of retinal flatmounts.RESULTS. Mice remaining in red-tinted cages had a significantly greater PRL thickness than those housed in untinted cages at all time points. Red housing also led to a highly significant rescue of retinal function as determined by both dark-and light-adapted ERG responses. IHC further revealed a dramatic benefit on cone morphology and number in the red-as compared with the clear-housed group.CONCLUSIONS. Limitation of short-wavelength light exposure significantly slows degeneration in the Rho(P23H/+) mouse model. Red filters may represent a cost-effective and low-risk treatment for patients with rod-cone dystrophy in whom a sectoral phenotype is noted.