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Christian Grimm, Andreas Wenzel, Theodore P. Williams, Pascal O. Rol, Farhad Hafezi, Charlotte E. Remé; Rhodopsin-Mediated Blue-Light Damage to the Rat Retina: Effect of Photoreversal of Bleaching. Invest. Ophthalmol. Vis. Sci. 2001;42(2):497-505. doi: https://doi.org/.
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purpose. Acute white-light damage to rods depends on the amount of rhodopsin available
for bleaching during light exposure. Bleached rhodopsin is
metabolically regenerated through the visual cycle involving the
pigment epithelium, or photochemically by deep blue light through
photoreversal of bleaching. Because photoreversal is faster than
metabolic regeneration of rhodopsin by several orders of magnitude, the
photon catch capacity of the retina is significantly augmented during
blue-light illumination, which may explain the greater susceptibility
of the retina to blue light than to green light. However, blue light
can also affect function of several blue-light–absorbing enzymes that
may lead to the induction of retinal damage. Therefore, this study was
conducted to test whether rhodopsin and its bleaching intermediates
play a role in blue-light–induced retinal degeneration.
methods. Eyes of anesthetized rats and mice that did or did not contain
rhodopsin were exposed to green (550 ± 10 nm) or deep blue
(403 ± 10 nm) light for up to 2 hours. Rats with nearly
rhodopsinless retinas were obtained by bleaching rhodopsin in animals
with inhibited metabolic rhodopsin regeneration—that is, under
halothane anesthesia. In addition, Rpe65 −/− mice that are completely
without rhodopsin were used to test the susceptibility to blue-light
damage of a rodent retina completely devoid of the visual pigment.
Effects of illumination on photoreceptor morphology were assessed 24
hours or 10 days thereafter by morphologic and biochemical methods.
results. Exposure to blue light resulted in severe retinal damage and activation
of the transcription factor AP-1 in rats. In contrast, green light had
no effect. When rhodopsin was almost completely bleached by short-term
green-light exposure while metabolic regeneration (but not
photoreversal) was prevented by halothane anesthesia, blue-light
exposure induced distinct lesions in rat retinas. When both metabolic
rhodopsin regeneration and photoreversal of bleaching were almost
completely inhibited, blue-light exposure caused only very moderate
lesions. When mice without rhodopsin were exposed to blue light, no
damage occurred, in contrast to wild-type control mice.
conclusions. Short time exposure to blue light has deleterious effects on retinal
morphology. Because damage was observed only in the presence of the
visual pigment, blue-light–induced retinal degeneration is rhodopsin
mediated. Absorption of blue light by other proteins is not sufficient
to induce light damage. Photoreversal of bleaching, which occurs only
in blue but not in green light, increases the photon-catch capacity of
the retina and may thus account for the difference in the damage
potential between blue and green light.
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