| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 From the Department of Ophthalmology, University Eye Clinic, Zurich, Switzerland; and the 2 Department of Biological Science, Florida State University, Tallahassee.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
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.
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
In rats, exposure to excessive levels of white light causes apoptotic cell death, not only of photoreceptors,13 but, with a short delay, also of the retinal pigment epithelium (RPE).14
Different wavelengths and different intensities of light have specific physical properties that can differently affect biologic molecules. There is a broad spectrum of light-damage experiments in which different parameters are applied so that strict comparisons are almost impossible (for review see Reference 15 ). In line with this diversity, several action spectra of light damage have been recorded for the retina. Williams and Howell16 reported an action spectrum that closely resembled the absorption spectrum of rhodopsin, suggesting that light of a wavelength of approximately 500 nm would be most effective in inducing light damage. In other studies, however, light of shorter wavelengths generally caused the most severe damage.17 18 19 20 To date, molecular mechanisms by which visible light of short wavelength damages the retina are unknown. It has been hypothesized that blue-light damage may occur by photosensitizing, oxygen-dependent processes that may affect photoreceptors and RPE similarly.21 22 In support of this view, the application of antioxidants such as dimethylthiourea results in a partial protection of the retina against light damage.23
Several chromophores have been suggested that may be involved in blue-light damage. Cytochrome oxidase is inhibited in the rat retina after exposure to blue light, suggesting reduced retinal metabolism after light exposure.24 25 26 Prostaglandin G/H synthase, in contrast, is activated after absorption of blue light, leading to peroxidation in the retina and to the production of superoxide radicals that may have the capacity to injure retinal tissue27 and induce apoptosis. Furthermore, the identification of a blue and ultraviolet light-absorbing opsin in the RPE28 renders it possible that excessive absorption of light by pigment epithelial cells could create a death signal that is transmitted to the photoreceptors.
In white light, the primary chromophore for light damage is rhodopsin.2 It has been shown that the rate of metabolic rhodopsin regeneration in the visual cycle that involves the transport of the chromophore to and from the RPE with isomerization and redox steps,29 30 sets the photon-catch capacity of a retina and is a major determinant in susceptibility to light damage.3 However, bleached rhodopsin may be regenerated, not only metabolically, but also photochemically. In vitro, visible light of short wavelength (blue light) can restore activatable rhodopsin by a process called photoreversal of bleaching.31 Recently, we have demonstrated that photoreversal of bleaching by blue light also occurs in the living rat eye.32 Because the photochemical reversal is extremely fast, it significantly increases the photon-catch capacity of rhodopsin in photoreceptors during a given light exposure. This may explain the greater susceptibility of the retina to blue light than to light of longer wavelength.
In the present study, we tested whether rhodopsin might be involved in blue-light–mediated damage to the rodent retina by using several experimental paradigms, including photoreversal of bleaching, inhibition of metabolic rhodopsin regeneration, and transgenic mice without rhodopsin.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
Light Exposure
Rats were dark adapted overnight (16 hours) and anesthetized
with a mixture of ketamine (75 mg/kg) and xylazine (23 mg/kg) or with
halothane (oxygen flow, 0.8 l/min, evaporator at position 1.5). Left
eyes of anesthetized rats were kept moist with Methocel (CibaVision,
Hergiswil, Switzerland) and exposed either to deep blue light (403 ± 10 nm) or to green light (550 ± 10 nm) for up to 120 minutes.
Mice were dark adapted overnight (16 hours) and their pupils dilated
with Cyclogyl (1%; Alcon, Fort Worth, TX) and phenylephrine (5%).
They were then anesthetized with halothane. During anesthesia, mice
were kept on a heating pad (set at 40°C) that was covered with a
tissue. After a postexposure period of 24 hours in darkness, animals
were killed for analysis or were put back into cyclic light for an
additional 9 days. The light exposure system consisted of a xenon arc
reflector lamp (230 V, 50 Hz, 120 W; Intralux MDR 100, Volpi;
Schlieren, Switzerland) with interference filters to eliminate UV and
infrared (IR) radiation and a liquid fiberoptic light guide (8 mm in
diameter) to the animal’s eye. The optical system included a switch
holder for blue (403 nm, bandwidth ±10 nm) or green (550 nm, bandwidth
±10 nm) interference filters (Fig. 1)
.
|
Microscopy and Damage Assessment
In dim red light, eye cups of enucleated rat eyes were prepared
and immersed in 2.5% glutaraldehyde in 0.1 M cacodylate buffer (pH
7.3) at 4°C. After 3 to 5 hours of fixation, the superior and
inferior central retina adjacent to the optic nerve was trimmed, and
fixation was continued in the same medium as before at 4°C
overnight.12
Mouse eyes were enucleated, fixed overnight
at 4°C in the glutaraldehyde-cacodylate buffer, and the superior and
inferior central areas of the retinas were trimmed.34
Retinal tissue was washed in cacodylate buffer, postfixed in osmium
tetroxide for 1 hour, dehydrated in increasing ethanol concentrations,
and embedded in Epon 812. For light microscopy, 0.5-µm sections were
stained with methylene blue and analyzed by microscope (Axiophot;
Zeiss, Oberkochen, Germany). Extent of light damage was assessed by
counting pyknotic nuclei in a 200-µm segment of the inferior
central retina (the most affected region in our setup). More than 80%
pyknotic nuclei: very severe damage (+++); 40% to 80% pyknotic
nuclei: severe damage (++); 5% to 40% pyknotic nuclei: damage (+);
below 5% pyknotic nuclei: no damage (-).
TUNEL Assay
Eyes were fixed in 2% paraformaldehyde for 2 hours at 4°C
followed by dehydration and paraffin embedding. TdT-mediated dUTP
nick-end labeling (TUNEL) was performed with modifications using an in
situ cell death detection kit (Boehringer–Mannheim, Mannheim, Germany)
on 5-µm paraffin sections. DNA strand breaks were labeled with
fluorescein and visualized with a fluorescein isothiocyanate (FITC)
filter, as described.34
DNA Fragmentation Analysis
Retinas were removed rapidly through a slit in the cornea and
frozen in liquid nitrogen. Retinal tissue was homogenized in 1 ml of 10
mM Tris (pH 8), 10 mM EDTA, and 10 mM NaCl. Sodium dodecyl sulfate
(SDS) was added to a final concentration of 0.5%, and proteins were
digested with proteinase K (0.2 mg/ml) at 37°C for 16 hours. Fresh
proteinase K was added (0.2 mg/ml) and incubation continued for 2 hours
at 50°C. The mixture was extracted once with
phenol-chloroform-isoamylalcohol (25:24:1) and twice with
chloroform-isoamylalcohol (24:1). NaCl (final concentration, 300 mM)
and EtOH (2.5 volumes) were added, and DNA was precipitated overnight
at -20°C. After centrifugation for 10 minutes at 4000g
(4°C), DNA was washed once with 70% EtOH and air dried for 1 hour at
room temperature. TE (10 mM Tris [pH 8] and 1 mM EDTA) was added (100
µl per retina), and DNA was allowed to rehydrate for 2 days at 4°C.
RNA was digested by the addition of 20 µg RNase A and incubation at
37°C for 1 hour. DNA concentration was determined by reading optical
density at 260 nm (OD260). Total DNA (10 µg)
was analyzed on a 1.5% agarose gel, stained with ethidium bromide,
visualized at 254 nm and compared with a 100-bp DNA ladder (Pharmacia
Biotech, Uppsala, Sweden).
Electrophoretic Mobility Shift Assay
For electrophoretic mobility shift assay (EMSA), nuclear
extracts were prepared as described previously for mice.8
Briefly, one retina was homogenized in 400 µl of 10 mM HEPES-KOH (pH
7.9), 1 mM ß-mercaptoethanol, and 1 mM dithiothreitol (DTT) in the
presence of protease inhibitors. After incubation on ice for 10 minutes
the homogenate was vortexed for 10 seconds and centrifuged. The pellet
was resuspended in 50 µl of 20 mM HEPES-KOH (pH 7.9), 25% glycerol,
420 mM NaCl, 1.5 mM MgCl2, 0.2 mM EDTA, 1 mM
ß-mercaptoethanol, and 1 mM DTT in the presence of protease
inhibitors and incubated on ice for 10 minutes. Cellular debris was
removed by centrifugation at 23,000g for 30 minutes at
4°C. Protein concentrations were determined using the Bradford
protein assay (Bio-Rad, Hercules, CA) with bovine serum albumin (BSA)
as standard.
EMSAs were performed as described.35
Briefly, two
oligonucleotides were annealed to form a double-stranded DNA coding for
an AP-1–specific (5'-AAG CAT GAG TCA GAC AC-3') DNA-binding sequence
(TPA response element; TRE). The annealed oligos were labeled using
polynucleotide kinase (Boehringer–Mannheim) and
32P-
ATP (Hartmann Analytic, Braunschweig,
Germany). For EMSA, 2 to 5 µg (5 µl) protein of nuclear extract was
incubated on ice for 20 minutes with 19 µl of 5 mM
MgCl2, 0.1 mM EDTA, 0.75 mM DTT, 7.5% glycerol,
and 0.05% NP-40 containing 24 µg BSA and 2 µg poly d (I-C)
(Boehringer–Mannheim). Radiolabeled oligonucleotide (1 µl) was
added, and incubation was continued for another 20 minutes. Protein-DNA
complexes were resolved at 150 V on a 6% native polyacrylamide gel
using 0.25x TBE as running buffer and visualized on x-ray film.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
Illumination with 3.1 mW/cm2 of 403-nm blue light for 30 minutes caused vesiculation of rod outer segments in the central region of the inferior part of the retina, as observed at 24 hours after exposure (Fig. 2 , white arrowheads). In most experiments, the superior retina was less affected by the light exposure (not shown). The reasons for the topologic differences are not clear but may be intrinsic to our experimental setup. Similar vesiculation was detected after illumination for 60 minutes, but, in addition, some pyknotic nuclei (white arrows) and apoptotic bodies (black arrows) were formed in the outer nuclear layer (ONL). Obviously, the threshold for blue-light–mediated damage was passed after 60 minutes of illumination (Fig. 2C) . The number of cells containing pyknotic nuclei increased dramatically after illumination for 90 (Fig. 2D) and 120 (Fig. 2E) minutes, with no photoreceptor cells surviving the blue-light illumination, as judged 10 days after exposure (Fig. 2F) . Cells of the pigment epithelium had also degenerated and were completely removed at this time point. Strikingly, rod outer segment (ROS) vesiculation was virtually absent in retinas that received a 90- or 120-minute exposure (Figs. 2D 2E ; see also Fig. 4 , Table 1 and discussion).
|
|
|
At 24 hours after exposure, blue-light, but not green-light, exposure resulted in the production of a DNA ladder after gel electrophoresis of genomic DNA (Fig. 3A ) and the formation of TUNEL-positive nuclei (Fig. 3B) . Both markers are indicative of ongoing apoptosis, and therefore, necrotic cell death may be excluded from blue-light–mediated retinal degeneration.
|
Essential Role of Rhodopsin in Blue-Light–Induced Photoreceptor
Apoptosis
Preservation of Retinal Morphology by the Absence of Bleachable
Rhodopsin in Rat Eyes.
Bleaching of rhodopsin was done by the illumination with low-level
green light (700 µW/cm2) for 1 hour. Such a
long exposure, in contrast to a 5-minute exposure32
(see
later description), not only caused complete bleaching but also allowed
the conversion of all bleaching intermediates to products that were no
longer photoreversible by blue light (data not shown). However, to
achieve this complete bleaching, rats had to be anesthetized with
halothane which almost completely prevents metabolic rhodopsin
regeneration.36
After complete bleaching, rhodopsin was
regenerated to 37% ± 4.4% of the dark value after 30 minutes
recovery in darkness (n = 5 retinas) and 83.3% ±
6.1% after 120 minutes (n = 5 retinas). However, in
animals anesthetized with halothane, the values after 30 minutes and
120 minutes were only 7.6% ± 1.8% (n = 4 retinas)
and 8.35% ± 2.3% (n = 4 retinas), respectively.
Consequently, our prebleaching protocol in animals anesthetized with
halothane resulted in the virtual absence of bleachable rhodopsin from
rat eyes during the subsequent illumination with doses of blue light
that have been shown to damage the retina in the normal situation (Fig. 2)
. At the end of the 1-hour preillumination period with green light
(700 µW/cm2), the interference filter was switched to
allow illumination with high-energy blue light (3.1
mW/cm2; Ganzfeld) and exposure continued for
additional 2 hours under halothane.
Control animals were anesthetized and illuminated with the same protocol, except that no green prebleaching was performed, and animals remained in darkness during the first hour of halothane anesthesia instead. Therefore, rhodopsin was present at normal levels at the beginning of the blue-light illumination in the control animals. Retinas almost devoid of rhodopsin showed only very moderate photoreceptor apoptosis (Fig. 5C ; most affected area is shown; Table 1 ), in contrast to retinas of the control animals that contained almost exclusively pyknotic photoreceptor nuclei after the treatment with blue light (Fig. 5B ; Table 1 ).
|
Extension of the exposure period to 1 hour resulted in another type of blue-light damage that affected the RPE. This damage was independent of rhodopsin, because it also occurred in rhodopsin-less Rpe65-/- mice. However, it is important to note that the photoreceptors still did not show condensation of nuclear chromatin (data not shown). The nature of these injuries in the RPE remains unknown for our experimental conditions but must involve mechanisms different from the ones for light-induced photoreceptor apoptosis. This is further supported by preliminary observations made in c-fos-/- mice. These mice not only are protected against white-light damage7 but also did not show photoreceptor apoptosis after blue-light exposure (data not shown). However, similar to the Rpe65-/- mice, c-fos-/- mice showed damage to the RPE after high-energy blue-light exposure (data not shown).
Blue-Light–Induced Retinal Damage after a Pre-Bleach of
Rhodopsin: Effect of Photoreversal of Bleaching
To test whether photograph regeneration would supply sufficient
rhodopsin molecules for light damage to occur, we exposed rat eyes to 5
minutes of green light (8.7 mW/cm2). After this
prebleaching, which reduced rhodopsin to 5.8% ± 1%
(n = 3), eyes were exposed to blue light for 60 (Fig. 6A
), 90 (Fig. 6B)
, or 120 minutes (Fig. 6C)
at an intensity of 3.1
mW/cm2. In control experiments, green-light
illumination continued for 120 minutes without switching to blue light
(Fig. 6D)
. Blue light induced photoreceptor apoptosis in a
dose-dependent manner, whereas green light did not affect retinal
morphology. Of note, light damage induced by blue light after
pre-exposure to green light was qualitatively indistinguishable from
damage without a preceding green-light bleaching (compare Figs. 2
and 6
). Because the switch from green to blue light occurred after 5
minutes, presumed intermediates of the bleaching process were still
present and could be photoreversed to rhodopsin by the following
blue-light exposure,32
in contrast to the experiment shown
in Figure 5
.
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
Several lines of evidence strongly indicate that blue-light–induced photoreceptor cell death is also rhodopsin mediated. As in white light, cell death of photoreceptors after blue-light exposure occurred through apoptosis, and blue-light damage involved activation of AP-1. The time course of this activation resembled the one seen after exposure to white light.8 Most important, however, rat retinas almost completely devoid of rhodopsin showed strongly reduced light damage after blue-light exposure, and mouse photoreceptors without rhodopsin were completely protected against blue-light exposure. Therefore, other blue-absorbing molecules, such as prostaglandin synthase27 and cytochrome oxidase,24 26 may play only minor roles as primary light receptors in the mediation of photoreceptor apoptosis by blue light. Similarly, we assume that lipid peroxidations and production of free radicals by light do not suffice to induce immediate photoreceptor death in the absence of rhodopsin. Alternatively, formation of such molecules could depend on the absorption of large numbers of photons by rhodopsin and thus be secondary effects. Therefore, we suggest, that rhodopsin is the main chromophore necessary for blue-light–induced retinal degeneration. Intracellular signaling pathways may be very similar in blue- and white-light conditions.
However, because high-energy blue light could damage cells of the RPE in a rhodopsin-independent way (data not shown), the molecules and mechanisms described above may be relevant for this latter type of lesion. Other molecules that strongly absorb light in the blue range include lipofuscin and melanin.37 38 Although melanin may not have an essential role in light damage,39 40 lipofuscin, or its main component A2E, may be a candidate for the mediation of light damage to the RPE. Both, cell toxicity41 and inhibition of mitochondrial function by A2E are increased by light exposure.42 However, rhodopsin, one of the precursors thought to be involved in the formation of A2E is missing in Rpe65-/- mice.43 It is unlikely that these mice contain A2E in the RPE and therefore that A2E may be involved in the mediation of blue-light damage to the RPE in the Rpe65-/- mice. An alternative explanation for the observed RPE damage would be thermal effects. However, long-wavelength and heat-creating light was eliminated in our illumination system by the use of an interference filter (see the Materials and Methods section). Clearly, the analysis of blue-light–mediated damage to the RPE needs further investigations. With Rpe65-/- and c-fos-/- mice, both of which resist blue-light damage to the photoreceptors but not to the RPE, there are two suitable model systems used to analyze molecular and cellular mechanisms of light-induced RPE damage in vivo without the interference of photoreceptor cell death.
Effect of Photoreversal of Bleaching on Light-Induced Retinal
Degeneration
To restore bleachable rhodopsin, a retina exposed to blue light
does not depend on the slow metabolic regeneration in the visual cycle
alone. Blue light, by the extremely rapid process of
photoreversal,31
can photochemically regenerate rhodopsin
in vivo from long-lived bleaching intermediates, probably
metarhodopsin MII.32
44
Although blue light is less
efficiently absorbed by rhodopsin than light at approximately 500 nm,
photoreversal by blue light nevertheless dramatically increases the
photon-catch capacity of the retina32
and thus increases
its susceptibility to light damage. Therefore, photoreversal of
bleaching may indeed play a significant role in mediating damage by
visible light of short wavelength. When rhodopsin was prebleached to
near completion with nondamaging light (green), immediate exposure to
blue light was capable of restoring sufficient rhodopsin for the
absorption of enough photons required for light damage to occur.
However, this appeared to be possible only when reversible
intermediates of the bleaching process were still present in
photoreceptors, suggesting that the effect is specific and depends on
rhodopsin.
In contrast, when green light is used for exposure, supply of unbleached rhodopsin exclusively depends on metabolic regeneration in the visual cycle. Thus, in green light it would take much longer time to absorb deleterious amounts of photons than in blue light. Our results show that even short periods of blue-light illumination induced photoreceptor apoptosis, whereas green light had no effect on retinal morphology. Nevertheless, we cannot exclude that illumination with green light in the range of several hours or days would eventually lead to retinal damage in our experimental system, provided that metabolic regeneration is functioning. Indeed, other experimental setups use green light to induce retinal damage.40 45 However, four major differences between the setup used here and that used by others should be considered: 1) We used narrow-band green light of high intensity (in milliwatts), whereas others used broad-band green light of low intensity (in microwatts) containing a small proportion of light below a wavelength of 500 nm.1 45 Green light, as applied in the present study, is not able to photoreverse rhodopsin in vivo.32 Broad-band green light reaching below a wavelength of 500 nm, however, may enable some photoreversal. 2) We used short-term exposure in contrast to the long-term exposure used in other studies. 3) In the present study, anesthetized rats were exposed in contrast to free-moving animals used by others, and consequences of anesthesia for light damage have not been studied in full detail yet. 4) Light exposure resulted in damage primarily of the inferior hemisphere of the retina comparable to some forms of retinitis pigmentosa, whereas other studies point to the superior hemisphere as the more sensitive region for light damage (for review, see Reference 21 ). This again demonstrates differences between the individual experimental setups.
The phenomenon of photoreversal of bleaching may explain why light of shorter wavelength is generally more damaging to the retina than light of longer wavelengths. Because white light contains light of all wavelengths, we suggest that the emission spectrum of white light bulbs is highly critical, not only for the induction of retinal damage in laboratory animals, but also for safety in human eyes.
ROS Vesiculation as Indicator of Photoreceptor Survival?
Illumination of a retina with blue light for 30 minutes caused
vesiculation of ROS observed 24 hours after lights off. The absence of
pyknotic nuclei suggests that the cells did not activate the apoptotic
death program. Increasing the illumination time to 60 minutes resulted
in similar ROS vesiculations, but in addition, several photoreceptor
nuclei appeared condensed, indicating ongoing apoptosis. Extending the
illumination time to 90 and 120 minutes increased the number of
pyknotic nuclei dramatically. In these tissues, no ROS vesiculation was
detected (Figs. 2B
2C
2D
2E)
. This phenomenon was especially
pronounced in experiments that were performed without the Ganzfeld
device (Fig. 4)
. In this situation, we observed hot spots of light
damage with sharp borderlines to the neighboring tissue. It was
striking that in areas with almost exclusively pyknotic nuclei, no ROS
vesiculation was observed, whereas in areas immediately adjacent, ROS
vesiculation was very pronounced, but almost no pyknotic nuclei were
detectable. This observation suggests that ROS vesiculations and the
formation of pyknotic nuclei could be mutually exclusive. Moderate
light levels, which do not induce cell death, would cause ROS
vesiculations that will be repaired,46
whereas high light
levels would cause pyknotic nuclei and cell death. The induction of
programmed cell death may therefore prevent ROS vesiculation or vice
versa.
In earlier studies we found release of arachidonic acid (AA), DHA, and leukotriene B4, after light exposure (reviewed in Reference 15 ). We do not know whether they are involved in the vesiculation of ROS or the apoptosis of photoreceptors. Nevertheless, we might speculate that at moderate levels, these mediators could destabilize membranes leading to ROS vesiculation but might induce apoptosis if they surpass a critical concentration. However, molecular mechanisms leading to either ROS vesiculations or apoptosis induction remain to be elucidated.
|
Conclusions |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
|
Acknowledgements |
|---|
|
Footnotes |
|---|
Submitted for publication June 7, 2000; revised August 17 and September 29, 2000; accepted October 6, 2000.
Commercial relationships policy: N.
Corresponding author: Christian Grimm, Department of Ophthalmology, University Eye Clinic, Frauenklinikstrasse 24, CH-8091 Zurich, Switzerland. cgrimm{at}opht.unizh.ch
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  I. Iandiev, A. Wurm, M. Hollborn, P. Wiedemann, C. Grimm, C. E. Reme, A. Reichenbach, T. Pannicke, and A. Bringmann Muller Cell Response to Blue Light Injury of the Rat Retina Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3559 - 3567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Schmitz-Valckenberg, L. Guo, A. Maass, W. Cheung, A. Vugler, S. E. Moss, P. M. G. Munro, F. W. Fitzke, and M. F. Cordeiro Real-Time In Vivo Imaging of Retinal Cell Apoptosis after Laser Exposure Invest. Ophthalmol. Vis. Sci., June 1, 2008; 49(6): 2773 - 2780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kanan, G. Moiseyev, N. Agarwal, J.-X. Ma, and M. R. Al-Ubaidi Light Induces Programmed Cell Death by Activating Multiple Independent Proteases in a Cone Photoreceptor Cell Line Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 40 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M A Mainster Violet and blue light blocking intraocular lenses: photoprotection versus photoreception Br. J. Ophthalmol., June 1, 2006; 90(6): 784 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Reme The Dark Side of Light: Rhodopsin and the Silent Death of Vision The Proctor Lecture Invest. Ophthalmol. Vis. Sci., August 1, 2005; 46(8): 2672 - 2682. [Full Text] [PDF]
|
|
|
|
 |
|
 O. Strauss The Retinal Pigment Epithelium in Visual Function Physiol Rev, July 1, 2005; 85(3): 845 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Mainster Intraocular Lenses Should Block UV Radiation and Violet but Not Blue Light Arch Ophthalmol, April 1, 2005; 123(4): 550 - 555. [Full Text] [PDF]
|
|
|
|
|
|
M A Mainster and J R Sparrow How much blue light should an IOL transmit? Br. J. Ophthalmol., December 1, 2003; 87(12): 1523 - 1529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. Gordon, D. M. Casey, W. J. Lukiw, and N. G. Bazan DNA Damage and Repair in Light-Induced Photoreceptor Degeneration Invest. Ophthalmol. Vis. Sci., November 1, 2002; 43(11): 3511 - 3521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Thomson, Y. Toyoda, A. Langner, F. C. Delori, K. M. Garnett, N. Craft, C. R. Nichols, K. M. Cheng, and C. K. Dorey Elevated Retinal Zeaxanthin and Prevention of Light-Induced Photoreceptor Cell Death in Quail Invest. Ophthalmol. Vis. Sci., November 1, 2002; 43(11): 3538 - 3549. [Abstract] [Full Text] [PDF]
|
|
50% pyknotic nuclei; E: >90%
pyknotic nuclei). (C) Mixture of ROS vesiculation, pyknotic
nuclei, and apoptotic bodies (black arrows) was observed.
(F) Degenerated photoreceptor cell layer and the RPE at +10
days. In contrast, green-light exposure did not affect photoreceptors
or the pigment epithelium. (G, H) Representative
sections of two to three independent experiments are shown. RIS, rod
inner segments. Scale bar, 25 µm.
