Sensitivity to retinal light damage and surgical blood oxygen levels

Increased oxygen levels decrease the threshold for photochemical retinal damage. We measured arterial oxygen levels in a group of ophthalmic surgical patients. As expected, levels exceeded unanesthetized measurements by one to two times. Based on experimental data, this could decrease the threshold for light-induced retinal damage during ophthalmic surgery by 40% to 50%. While the clinical implications of light-induced retinal damage in surgical eye patients are unclear, it is prudent to take steps to minimize light exposure during surgery.     

Effects of vitamin e, pentoxifylline and aprotinin on light-induced retinal injury

PURPOSE: A considerable amount of clinical and experimental evidence exists suggesting the involvement of reactive oxygen species (ROS) in the etiology of light-induced retinal injury. The aim of this study was to investigate the protective role of vitamin E, pentoxifylline (PTX) and aprotinin against light-induced retinal injury in guinea pigs. METHODS: Thirty adult male guinea pigs were divided into 5 groups of 6 animals each. The first group was used as control. The guinea pigs were kept in cyclic light for 2 weeks before the experiments. The animals were maintained in 12-hour light-dark cycles, before and after exposure to intense white fluorescent light, for as long as 12 h and then returned to cyclic light. Groups 3-5 received intraperitoneal injections of vitamin E, PTX and aprotinin, respectively. One eye of each animal was selected for histopathological evaluation and the other for biochemical assay. Retinal malondialdehyde (MDA) levels and the thickness of the outer nuclear layers were measured. RESULTS: The compounds had the following relationships: vitamin E more than PTX more than aprotinin in preventing light-induced retinal damage. All 3 gave significant protection against the formation of MDA. Retinas of all 3 treatment groups had been protected from light-induced injury. CONCLUSION: The intraperitoneal vitamin E, PTX and aprotinin supplementations may strengthen the antioxidant defense system because of decreased ROS, and these agents may play a role in treating light-induced retinal injury.     

Comparison of retinal vasodilator and constrictor responses in type 2 diabetes

Purpose: The retinal blood vessels provide a unique way to directly examine the human microvasculature, which is frequently damaged in individuals with diabetes. Previous studies have demonstrated that retinal flickering light-induced vasodilation and hyperoxia-induced vasoconstriction may operate by enhancing or reducing similar vasoregulatory factor(s), but a comparison between these two provocative stimuli in individuals with diabetes has not been studied. The purpose of the study was to examine the association between retinal flickering light-induced vasodilation and retinal hyperoxia-induced vasoconstriction in type 2 diabetic subjects and in healthy controls. Methods: Twenty men and women with type 2 diabetes and 10 men and women without diabetes between 21 and 75?years of age were recruited. Changes in retinal artery and vein diameters to flickering light and during hyperoxia (100% oxygen) stimuli were measured on the same visit using a noninvasive retinal imaging device (Dynamic Vessel Analyzer, Imedos Inc., Germany). Results: Compared with controls, diabetic subjects had impaired arterial vasodilator and vasoconstrictor responses to both flickering light and hyperoxia, respectively (both p?相似文献   

视网膜光损伤机制的研究进展

视网膜是一种高度专业化的组织,具有独特的结构及适应性,在所有不同类型的视网膜细胞中保持动态平衡对于维持视力至关重要。视网膜可能会暴露在各种环境损伤中,如光诱导的损伤,在进化过程中,视网膜细胞对各种损伤产生了适应性反应,这些反应共同恢复了细胞的动态平衡,并增加了组织对进一步损伤的抵抗力。然而过度光照则会导致视网膜组织内光感受器细胞、视网膜神经节细胞(RGC)、视网膜神经胶质细胞及视网膜色素上皮细胞(RPE)发生一系列病理改变,包括线粒体内活性氧(ROS)和Ca²⁺浓度增加、细胞凋亡、内质网应激、细胞自噬和炎症等,从而导致视网膜发生不可逆损伤。本文将对视网膜光损伤的发病机制和相关研究进展进行详细阐述,为未来防治视网膜光损伤提供研究方向。     

Susceptibility to retinal light damage in transgenic rats with rhodopsin mutations

PURPOSE: To determine relative light-induced retinal damage susceptibility in transgenic rats expressing mutations in the N- or C-terminal region of rhodopsin. METHODS: Heterozygous transgenic rats, including P23H sublines 2 and 3 and S334ter sublines 4 and 9, were reared in dim cyclic light or in darkness before visible light exposure starting at various times of the day or night. Before exposure to light, some rats were given the synthetic antioxidant dimethylthiourea (DMTU). At various times after intense light treatment, rats were killed for determinations of rhodopsin and retinal DNA recovery, DNA fragmentation patterns, and Northern blot analysis of retinal heme oxygenase (HO)-1 and interphotoreceptor retinol binding protein (IRBP). Rod outer segments (ROSs) were isolated for Western blot analysis of rhodopsin using N- and C- terminal-specific monoclonal antibodies. RESULTS: All rats incurred greater photoreceptor cell damage from exposure to light starting at 1 AM than from exposure at 5 PM. Among cyclic-light-reared rats, P23H line 3 animals were more susceptible to light-induced damage than P23H line 2 animals. S334ter rats exhibited retinal light damage profiles similar to those in normal rats. Dark-rearing potentiated retinal damage by light. However, dark-rearing alone prolonged photoreceptor cell life in P23H rats, but had no such effect in S334ter animals. DMTU pretreatment was effective in preventing or reducing light-induced retinal damage in all transgenic rats. S334ter rat ROSs contained the truncated form of rhodopsin. Intense light exposure resulted in DNA ladders typical of apoptotic cell death and the simultaneous induction of retinal HO-1 mRNA and reduced expression of IRBP. CONCLUSIONS: Light-induced retinal damage in transgenic rats depends on the time of day of exposure to light, prior light-or dark-rearing environment, and the relative level of transgene expression. Retinal light damage leads to apoptotic visual cell loss and appears to result from oxidative stress. These results suggest that reduced environmental lighting and/or antioxidant treatment may delay retinal degenerations arising from rhodopsin mutations.     

Light-induced maculopathy in cataract surgery

CASE REPORT: Case 1: An 82-year-old man who underwent an uncomplicated phacoemulsification and IOL implantation (Tecnis Z 9000 lens) in his right eye under topical anaesthesia. Surgery lasted 14 minutes. Case 2: A 60-year-old woman with bilateral advanced primary open angle glaucoma who underwent an uncomplicated phacoemulsification and IOL implantation (Tecnis Z 9000 lens) in her right eye under peribulbar anaesthesia. Surgery lasted 36 minutes. One month after surgery both patients noted a para-central scotoma and impaired vision. Fluorescein angiography in both cases revealed retinal pigment epithelial changes compatible with intra-operative light-induced maculopathy. DISCUSSION: Light-induced maculopathy has been reported following cataract surgery. Whether physical properties of these new polysiloxane lenses contribute to retinal susceptibility to phototoxicity under certain light conditions needs to be elucidated.     

Photic retinal injury from endoillumination during vitrectomy

We treated a patient who developed a paramacular area of light-induced retinal damage after endoscopic epimacular membrane removal. Postoperative color photographs showed complete absence of the membrane, but fluorescein angiography demonstrated a previously absent superior paramacular lesion consistent with a photic injury. Operative microscope illumination had been eliminated by corneal shielding, which implicated endoillumination as the source of injury. We recommend the following procedures to avoid this complication: careful planning of vitreous surgery for epimacular membrane removal; using filters; minimizing the length of surgery; keeping the light output low; maintaining maximal light pipe distance from the retina; eccentric orientation of the light pipe; and use of intermittent and variable site illumination techniques.     

The standing potential of the human eye reflects differences between upper and lower retinal areas

In 12 healthy subjects the "light peak" of the electrooculogram was measured following localized stimulation of various retinal locations. Significant differences in "light peak" amplitudes were found between central and peripheral stimulation, and at 10 deg eccentricity the "light peak" amplitudes were significantly larger following upper retinal stimulation than those elicited by lower retinal stimuli. In addition, the "light peak" amplitude produced by upper or lower retinal stimulation behaved differently when test light intensity increased. The upper retinal areas showed consistently a higher sensitivity to light intensity changes than the lower retinal areas. The "light peak" of the EOG is believed to index the rate of retinal metabolism elicited by light stimuli. Our findings show that upper retinal areas display a higher level of light-induced activity reflecting the interaction between the photoreceptors and the retinal pigment epithelium than lower retinal areas. The results are interpreted as a superiority of the upper over the lower retina and are related to other electrophysiological and functional differences between upper and lower retinal areas of man.     

Calpains are activated by light but their inhibition has no neuroprotective effect against light-damage

Calpain had been shown to be highly activated at one day after exposure to the damaging light (Perche et al. (2007)Caspase-dependent apoptosis in light-induced retinal degeneration. Invest Ophthalmol Vis Sci 48:2753–2759.), suggesting that they might play a critical role in photoreceptor apoptosis induced by light. Therefore in the present study we investigate the role of calpain in light-induced photoreceptor cell death. In a first set of experiments, untreated albino Wistar rats were sacrificed at 0, 2, 4, 6, 12, 24 h of light exposure and at one day after the light was turned off (D1) to measure retinal calpain activity and to study calpain expression. In a second set of experiments, after control electroretinograms (ERGs), rats were uninjected or injected intravitreally with DMSO or the calpain inhibitor Mu-Phe-hPhe-FMK, before being exposed to the damaging light for 24 h. ERGs were then recorded at one day (D1) and fifteen days (D15) after the end of light exposure. Rats were sacrificed at D1 for apoptotic cell detection or D15 for histological analysis (ONL thickness). Calpain activity and expression significantly increased in Untreated retinas, from 0 h to D1. DMSO has no effect on calpain activity. Mu-Phe-hPhe-FMK significantly inhibited retinal calpain activity by 85% at 2 h of light exposure and still 48% at D1. However, Mu-Phe-hPhe-FMK has no effect on light-induced retinal degeneration as evidence by equivalent loss of function, equivalent loss of photoreceptor cells and an equivalent number of apoptotic cells in Mu-Phe-hPhe-FMK and DMSO retinas. Therefore, calpains are up-regulated by light stress but they do not have a pivotal role in photoreceptor apoptosis.     

Calpains are activated by light but their inhibition has no neuroprotective effect against light-damage

Calpain had been shown to be highly activated at one day after exposure to the damaging light (Perche et al. (2007) Caspase-dependent apoptosis in light-induced retinal degeneration. Invest Ophthalmol Vis Sci 48:2753–2759.), suggesting that they might play a critical role in photoreceptor apoptosis induced by light. Therefore in the present study we investigate the role of calpain in light-induced photoreceptor cell death. In a first set of experiments, untreated albino Wistar rats were sacrificed at 0, 2, 4, 6, 12, 24 h of light exposure and at one day after the light was turned off (D1) to measure retinal calpain activity and to study calpain expression. In a second set of experiments, after control electroretinograms (ERGs), rats were uninjected or injected intravitreally with DMSO or the calpain inhibitor Mu-Phe-hPhe-FMK, before being exposed to the damaging light for 24 h. ERGs were then recorded at one day (D1) and fifteen days (D15) after the end of light exposure. Rats were sacrificed at D1 for apoptotic cell detection or D15 for histological analysis (ONL thickness). Calpain activity and expression significantly increased in Untreated retinas, from 0 h to D1. DMSO has no effect on calpain activity. Mu-Phe-hPhe-FMK significantly inhibited retinal calpain activity by 85% at 2 h of light exposure and still 48% at D1. However, Mu-Phe-hPhe-FMK has no effect on light-induced retinal degeneration as evidence by equivalent loss of function, equivalent loss of photoreceptor cells and an equivalent number of apoptotic cells in Mu-Phe-hPhe-FMK and DMSO retinas. Therefore, calpains are up-regulated by light stress but they do not have a pivotal role in photoreceptor apoptosis.     

白蒺藜对光损伤小鼠光感受器细胞的保护作用

目的 探讨白蒺藜对小鼠视网膜光损伤的保护作用.方法 采用10 000 lux白炽光光照30 min建立视网膜光损伤模型,将BALB/c小鼠分为正常对照组、模型组和治疗组,每组各6只.光照前0.5h治疗组腹腔注射白蒺藜水煎液100 μL(生药100mg/20 g),正常对照组和模型组腹腔注射等量生理盐水.光照后3h、7d分别通过OCT检测小鼠视网膜形态学改变;造模后7d处死小鼠,取眼球固定、包埋、切片进行HE染色,视紫红质和短波敏感视蛋白(short wave-length sensitivity opsin,M-opsin)的免疫荧光化学染色,观察视网膜病理改变情况.结果 正常对照组内外核层结构清楚、界限明显,视网膜视杆细胞内外节排列整齐;模型组视网膜结构层次模糊且外核层变薄,与正常对照组差异显著;治疗组小鼠视网膜结构与正常对照组没有显著差异.与正常对照组比较,模型组视紫红质和M-opsin表达降低,治疗组显著提高了视紫红质和M-opsin的表达.模型组较正常对照组视网膜外核层厚度显著变薄(P＜0.05);治疗组较模型组能显著性预防小鼠视网膜外核层变薄(P＜0.05).结论 小鼠视网膜光损伤模型造模成功,白蒺藜对光损伤视网膜具有显著的保护作用.     

A novel isoform of acetylcholinesterase exacerbates photoreceptors death after photic stress

PURPOSE: To study the involvement of stress-induced acetylcholinesterase (AChE) expression in light-induced retinal damage in albino rats. METHODS: Adult albino rats were exposed for 24 hours to bright, damaging light. AChE expression was monitored by in situ hybridization, by histochemistry for AChE activity, and by immunocytochemistry. An orphan antisense agent (Monarsen; Ester Neurosciences, Ltd., Herzlia Pituach, Israel) was administered intraperitoneally to minimize light-induced AChE expression. The electroretinogram (ERG) was recorded to assess retinal function. RESULTS: Twenty-four-hour exposure to bright light caused severe reduction in the ERG responses and augmented expression of mRNA for the "read-through" variant of AChE (AChE-R) in photoreceptor inner segments (IS), bipolar cells, and ganglion cells. AChE activity increased in IS. The expressed AChE protein was a novel variant, characterized by an extended N terminus (N-AChE). Systemic administration of the orphan antisense agent, Monarsen, reduced the photic induction of mRNA for AChE-R, and of the N-AChE protein. Rats exposed to bright, damaging light and treated daily with Monarsen exhibited larger ERG responses, relatively thicker outer nuclear layer (ONL), and more ONL nuclei than did rats exposed to the same damaging light but treated daily with saline. CONCLUSIONS: The findings indicate that the photic-induced novel variant of AChE (N-AChE-R) may be causally involved with retinal light damage and suggest the use of RNA targeting for limiting such damage.     

Protective effects of soft acrylic yellow filter against blue light-induced retinal damage in rats

Recently, a yellow intraocular lens (IOL) was developed for the purpose of reducing potential blue light-induced retinal damage after cataract surgery. However, the effect of yellow filters on retinal protection remains to be clarified. To test the protective effects of yellow filters on blue light-induced retinal damage, a yellow and a clear soft acrylic filter were attached to the right and left eyes, respectively, of albino rats and exposed to 4.5 k lux blue fluorescent lights with peak wavelength at 420 nm (ranging 380-500 nm; short blue) or 446 nm (ranging 400-540 nm; long blue) for 6h. To assess retinal damage, the electroretinogram (ERG) was recorded at 7 days, outer nuclear layer (ONL) thickness and area were measured at 7 days, apoptosis was analyzed by TUNEL staining at 24 h, and the level of lipid peroxidation in retinas was assessed by Western dot blots using specific antibodies against 4-hydroxynonenal (4-HNE)- and carboxyethylpyrrole (CEP)-modified proteins immediately after light exposure. After short blue light exposure, a- and b-wave ERG amplitudes and the ONL thickness at 1-2.5 mm inferior and 0.5-2.5 mm superior to optic nerve head (ONH) were significantly reduced. TUNEL staining in the ONL at 0-2 mm inferior and 1-2 mm superior to the ONH, and retinal levels of 4-HNE- and CEP-modified proteins were significantly increased in the clear filter-covered eyes compared to yellow filter-covered eyes. After long blue light exposure, the only difference seen was a greater ONL thickness at 1.5 mm superior to the ONH in yellow filter-covered eye. Transmission of light through the yellow filter was 58% for short blue and 89% for long blue compared to the clear filter. The ONL area was not different between clear filter-covered and -uncovered eyes after exposure to short or long blue light. Given the results, yellow IOL material protects the retina against acute shorter wavelength blue light exposure more effectively than the clear IOL material.     

AcrySof Natural filter decreases blue light-induced apoptosis in human retinal pigment epithelium

Purpose The effect of AcrySof filter (UV light-filtering chromophore; Alcon) and AcrySof Natural filter (UV- and blue light-filtering chromophores) on blue light-induced apoptosis in human retinal pigment epithelial (RPE) cells was evaluated. Design Laboratory investigation Clinical relevance Acrysof Natural filter reduces the blue-light toxicity in RPE cells and may have a positive impact on age-related macular degeneration (AMD). Methods RPE cells were exposed to blue light (430–450 nm) in the presence of either the AcrySof (UV only) filter or Acrysof Natural (UV and blue light) filter for 10 days. The rate of apoptosis was analyzed. Results Blue light induced significant apoptosis in RPE cells. AcrySof Natural filter significantly reduced the blue light-induced apoptosis when compared to AcrySof filter. The amount of blue-light energy reaching the cells with the AcrySof filter was 4.25 mW/cm² and with the AcrySof Natural filter was 2.5 mW/cm². Conclusions AcrySof Natural filter significantly reduced blue light-induced apoptosis. This was most likely due to its filtering effect on blue wavelength light, which reduces the energy that reaches the cells. In patients with cataract who are at a high risk for AMD, the implantation of a blue light-filtering intraocular lens may be considered. Supported in part by Alcon Laboratories and Research to Prevent Blindness. None of the authors have a proprietary interest.     

Failure of ascorbate to protect against broadband blue light-induced retinal damage in rat

· Background: Excessive generation of free radicals due to light absorption is proposed as the most likely mechanism for photochemical retinal damage. The observed reduction of green light-induced retinal injury after ascorbate treatment is believed to be an antioxidative effect. The aim of the present study was to evaluate the possible protection of ascorbate against blue light-induced photoreceptor damage. · Methods: Cyclic light-reared albino rats were injected intraperitoneally with either ascorbate (1 mg/g body weight) or, as placebo, physiological saline 24 h before and just prior to exposure to blue light. After 20–22 h of dark adaptation, two groups of the rats were exposed in pairs to the blue light (400–480 nm) for 6 h at an average irradiance of 0.7 W/m² in the cage. Six days after light exposure, all rats were killed and retinal samples were analyzed. · Results: Diffuse blue light irradiation resulted in an uneven distribution of damage in the retina. As judged from the pathological changes in the retina irradiated, no microscopic difference was observed between the two groups. The preserved thickness of the outer nuclear layer was on average 61.3% in the ascorbate-treated and 66.4% in the placebo-treated group. The photoreceptor loss was not significantly different between the two groups. · Conclusion: The ascorbate did not protect the retina from blue-light induced damage. This favors the assumption that the mechanisms for blue light-induced retinal damage might differ from that for green light. Received: 13 October 1998 Revised version received: 22 January 1999 Accepted: 18 February 1999     

Melatonin increases photoreceptor susceptibility to light-induced damage.

Melatonin is an indolamine hormone synthesized in the retina and pineal gland. It is thought to act as a paracrine neurohormone in the mammalian retina. Pinealectomy has been shown to protect photoreceptors from light-induced damage, and melatonin treatment has been reported to increase the degree of photoreceptor damage in albino rats. To determine how melatonin influences photoreceptor survival, the effect of melatonin administration on light-induced retinal damage was studied. Melatonin was administered to albino rats by intraperitoneal injections at various times before or after light exposure. The rats were exposed to high-intensity illumination (1600 lux) for 24 hr to induce photodamage, then returned to cyclic lighting for 12 days. After this, they were killed, and their eyes were removed and examined histologically. Measurements of the outer nuclear layer (ONL) thickness were taken at 12 different loci around the circumference of the retinal sections. The animals that received daily melatonin injections (100 micrograms) in the late afternoon (3 hr before lights off) for 1-3 days before photodamage showed an approximate 30% greater reduction compared with sham control animals in ONL thickness in the superior quadrant, the area most susceptible to light damage. Melatonin injections given after the photodamage did not affect ONL thickness. Although retinal susceptibility to light damage varied with time of day, the degree to which melatonin increased the degree of damage appeared unaffected by the time of day. These results suggest that melatonin may be involved in some aspects of photoreceptor sensitivity to light damage.     

The diurnal susceptibility of rat retinal photoreceptors to light-induced damage

Exposure of albino rats to high intensity light results in rapid, graded loss of photoreceptors. The hormonal status and age of an animal at the time of exposure affect the severity of light-induced retinal damage. The adrenal axis and pituitary hormones (prolactin) have been demonstrated previously to affect the degree of cell death in the retina. Because circadian rhythms for adrenal and pituitary secretion have been demonstrated in the rat, a series of experiments was undertaken to determine if a diurnal pattern of retinal susceptibility to light damage exists which might be related to endogenous endocrine rhythms. Male Sprague-Dawley rats were exposed to 4 hr of high intensity fluorescent light for 8 consecutive days during different phases of the 14:10 hr light: dark animal room light cycle. Morphometric analysis performed at the light microscopic level 2 weeks after exposure demonstrated a differential susceptibility to light-induced cell death depending upon the period during the light-dark cycle when animals received their daily light exposure. Neuronal cell death was confined to the outer nuclear layer as previously described. The retinas of animals exposed during the middle of the dark period or during the first 5 hr of the light period were significantly more damaged than the retinas of animals exposed during the last 9 hr of the light period. Control groups for the relative amounts of dark-adaptation between groups suggested that the diurnal susceptibility to light damage was not solely dependent upon the degree of dark adaptation. These results demonstrate a diurnal susceptibility of photoreceptors to light-induced cell death.     

Neuroprotection of photoreceptors by minocycline in light-induced retinal degeneration

PURPOSE: Microglial cells have been found to play pivotal roles in various neuronal degenerative diseases such as Parkinson's and Alzheimer's diseases. Minocycline, a microglial inhibitor, has recently been shown to be neuroprotective in various models of cerebral ischemia and degenerative diseases of the brain. This study was conducted to evaluate the neuroprotective effect of minocycline and the role of microglia in light-induced retinal degeneration. METHODS: BALB/cJ mice were exposed to intense green light for 3 hours and observed during 1, 3, or 7 days of dark recovery. The animals received intraperitoneal injections of minocycline or vehicle 1 day before exposure to light for 2, 4, or 8 days, depending on the periods of survival. Morphologic, morphometric, immunohistochemical, and electrophysiological studies were performed to evaluate the efficacy of minocycline in the amelioration of light-induced retinal degeneration and the possible involvement of microglial cells. RESULTS: Minocycline treatment provided marked amelioration in the loss of photoreceptors in light-induced retinal degeneration, as evidenced by morphologic, morphometric, and electrophysiologic criteria. Morphologically, the minocycline-treated group showed markedly better preservation of the outer retina after exposure to light. Morphometrically, at 7 days after exposure to light, in the minocycline-treated animals, 89.1% of the normal-appearing photoreceptor nuclei remained, but in the retinas of the vehicle-control group only 38.0% of these nuclei remained. This difference was statistically significant (P < 0.001). At 7 days after exposure to light electroretinography (ERG) showed that minocycline significantly preserved the amplitudes of dark-adapted a- and b-wave and light-adapted b-wave, which were all significantly reduced after exposure to light. Concomitant with this protective effect, at 3 days after exposure to light, the CD11b(+) microglial cells in the outer nuclear layer (ONL) and subretinal space in the minocycline-treated group were significantly decreased (by 63.5%) when compared with those in the light-exposed, vehicle-treated control group (P < 0.01). CONCLUSIONS: Minocycline is neuroprotective against light-induced loss of photoreceptors, possibly through the inhibition of retinal microglial activation.