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A. L. Lyubarsky, E. N. Pugh, Jr.; Retinoid Cycle in the Eyes of Normal and Nrl-/- Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4791.
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The existence of a "cone retinoid cycle" characterized by synthesis of 11-cis retinoids inside the retina rather than in RPE has been demonstrated in experiments with cone-dominated chicken and ground squirrel eyes. To investigate whether a cone-specific retinoid cycle functions in rod-dominated species we examined the visual cycle in Nrl-/- mice, which lack rods and whose photoreceptors are all cones.
Nrl-/- mice inbred in the C57Bl/6J background or control animals were dark-adapted overnight, exposed to a short (6-60 s) intense illumination estimated to produce 95-99% bleach of respectively cone S pigment or rhodopsin, allowed to recover in dark, sacrificed at certain time points in recovery; and retinoid contents of either whole eyes or isolated retinas determined.
In wild-type mice 11-cis retinal (11RAL) was regenerated in a linear manner at least up to the moment of ~50% regeneration at a rate of ~0.6% min-1. 11RAL regeneration in Nrl-/- mice was a biphasic process with approximately even contributions from both phases. The first (fast) phase was an exponential rise to the maximum equivalent to regeneration of ~1/2 of the dark 11RAL contents with the rate constant of ~0.13 min-1 and estimated corresponding initial 11RAL production rate of ~5 pmol/min per eye. Small amounts of retinyl esters were found in isolated retinas during the first 15 min of regeneration but disappeared thereafter. The slow phase represented a linear (zero order) production of 11RAL at a rate of ~0.2% of initial contents per min (~0.2 pmol/min per eye) and was characterized by absence of retinyl esters in the retina and high abundance of them in the RPE.
In the eyes of Nrl-/- mice regeneration of cone visual pigments branches in an approximately 1:1 ratio along 2 pathways differing in speed. The initial rate of 11RAL production is 25-30 times higher in the faster than in the slower process. Since during the first ~15 min of recovery retinyl esters could be found in the retina, the fast phase may represent a "cone" retinoid cycle contained inside the retina. The slower process, whose rate is closer to that exhibited by rods, may correspond to the traditional "rod" visual cycle, which involves 11RAL synthesis in the RPE.
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