The Experts below are selected from a list of 135 Experts worldwide ranked by ideXlab platform
Glyn Chidlow - One of the best experts on this subject based on the ideXlab platform.
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effects of a conventional Photocoagulator and a 3 ns pulse laser on preconditioning responses and retinal ganglion cell survival after optic nerve crush
2014Co-Authors: Osam Shibeeb, John P M Wood, Robert J Casson, Glyn ChidlowAbstract:Previous research has demonstrated that laser photocoagulation treatment of the monkey retina affords protection against experimental glaucoma-induced retinal ganglion cell (RGC) loss in areas overlying laser spots. The underlying mechanism is unknown, but it is conceivable that the laser acted as a preconditioning stimulus, inducing localised, endogenous production of survival factors. The related purposes of the current study were firstly to examine whether preconditioning pathways are activated by either a conventional Photocoagulator (CW) laser or a photoreceptor-sparing, short-pulse duration (2RT) laser in the rat retina, and secondly, to examine whether such preconditioning with either laser improves RGC survival after optic nerve (ON) crush. Pigmented rats were randomly assigned to one of three groups: sham, CW, 2RT. For the preconditioning study, laser spots were applied randomly to each retina in the posterior hemisphere of the eye taking care to avoid major blood vessels. Animals were killed at 6 h, 1d, and 7d after laser treatment, then analysed by qPCR, immunohistochemistry or Western immunoblotting. For the neuroprotection study, laser spots were administered to the mid-central retina of the right eye. The left eye served as a control. In two experiments, rats were lasered either 24 h or 7 days before ON crush, then killed a further 7 days later. Wholemount retinas were prepared and double labelling immunofluorescence performed. Nestin labelling allowed visualization of laser spots. Brn3a labelling identified viable RGCs. Photomicrographs of Brn3a labelling were taken in areas overlying nestin-positive laser spots. Quantification of Brn3a RGCs was then performed. Both the CW and 2RT lasers induced local glial cell activation. Moreover, both lasers induced localized upregulations of a number of well-documented (CNTF, FGF-2 Hsp27, pAKT) or putative (cFOS, ATF-3, IL-6) RGC survival factors. However, neither laser caused sustained increases in other factors associated with neuronal preconditioning, such as BDNF, Hsp70, IGF-1, bcl-2, and nitric oxide synthase. As regards neuroprotection, analysis of the data revealed that ON crush resulted in the loss of approximately 70% of Brn3a-labelled RGCs after 1 week. Neither the CW nor the 2RT laser augmented Brn3a-positive RGC survival in areas overlying and neighbouring laser spots. This was the case irrespective of whether lasering occurred 1 or 7 days before the ON crush. Our results showed that the CW and 2RT lasers both stimulated de novo synthesis of certain genes that are well-known RGC survival factors and/or that have been implicated in preconditioning-induced neuroprotection studies. Despite these findings, neither laser augmented survival of RGCs when delivered prior to ON crush.
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glial cell and inflammatory responses to retinal laser treatment comparison of a conventional Photocoagulator and a novel 3 nanosecond pulse laser
2013Co-Authors: Glyn Chidlow, Malcolm Plunkett, Osam Shibeeb, Robert J Casson, John P M WoodAbstract:Purpose Retinal laser photocoagulation represents a major treatment strategy for the management of diabetic macular edema (DME). However, the thermal nature of this procedure defines that collateral tissue injury result, meaning that it cannot be used near the fovea centralis. We studied inflammatory and glial responses resulting from treatment of rats with a conventional laser and with a novel short-duration, nonthermal laser (retinal regeneration therapy [2RT]) at clinically relevant energy levels. Methods Pigmented Dark Agouti rats were treated with either a conventional thermal continuous wave (CW; 532-nm, 100-ms pulse duration) or a short-pulse (2RT; 532-nm, Q-switched, 3-ns pulse) laser. Settings were at visible threshold for the CW laser (12.7 J/cm(2)/pulse) and at supra- and subvisible thresholds for the 2RT laser ("high," 2RT-H, 163 mJ/cm(2)/pulse; "low," 2RT-L, 109 mJ/cm(2)/pulse). Rats were killed at various subsequent time points. Samples were processed for histology, immunohistochemistry, RT-PCR, and Western blotting. Results The CW laser caused outer retinal lesions that were associated with photoreceptor death, astrocyte and Muller cell activation, and infiltration of macrophages and neutrophils. Furthermore, inflammatory cytokines, heat shock proteins, endogenous trophic factors, and matrix metalloproteinases were induced. In comparison, all of these changes were drastically attenuated when the 2RT laser was used, particularly at the subthreshold setting. Conclusions The conventional laser produced marked retinal damage and cellular responses consistent with an inflammatory response to thermal injury. In contrast, the 2RT laser produced negligible retinal damage and cellular responses at clinically relevant settings. These results may have important implications for the treatment of retinal disease.
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retinal damage profiles and neuronal effects of laser treatment comparison of a conventional Photocoagulator and a novel 3 nanosecond pulse laser
2013Co-Authors: John P M Wood, Osam Shibeeb, Malcolm Plunkett, Robert J Casson, Glyn ChidlowAbstract:PURPOSE: To determine detailed effects to retinal cells and, in particular, neurons following laser photocoagulation using a conventional 532 nm Nd:YAG continuous wave (CW) laser. Furthermore, to determine whether a novel 3 ns pulse laser (retinal regeneration therapy; 2RT) could specifically ablate retinal pigment epithelium (RPE) cells without causing collateral damage to other retinal cells. METHODS: Adult Dark Agouti (DA) rats were separated into four groups: control, CW laser (12.7 J/cm(2)/pulse, 100 ms pulse duration), or 3 ns pulse 2RT laser at one of two energy settings ("High," 2RT-H, 163 mJ/cm(2)/pulse; "Low," 2RT-L, 109 mJ/cm(2)/pulse). Animals were treated and killed after 6 hours to 7 days, and retina/RPE was analyzed by histologic assessment, Western blot, polymerase chain reaction, and immunohistochemistry. RESULTS: Both lasers caused focal loss of RPE cells with no destruction of Bruch's membrane; RPE cells were present at lesion sites again within 7 days of treatments. CW and 2RT-H treatments caused extensive and moderate damage, respectively, to the outer retina. There were no obvious effects to horizontal, amacrine, or ganglion cells, as defined by immunolabeling, but an activation of PKCα within bipolar cells was noted. There was little discernible damage to any cells other than the RPE with the 2RT-L treatment. CONCLUSIONS: Conventional laser photocoagulation caused death of RPE cells with associated widespread damage to the outer retina but little influence on the inner retina. The novel 3 ns 2RT laser, however, was able to selectively kill RPE cells without causing collateral damage to photoreceptors. Potential benefits of this laser for clinical treatment of diabetic macular edema are discussed.
John P M Wood - One of the best experts on this subject based on the ideXlab platform.
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effects of a conventional Photocoagulator and a 3 ns pulse laser on preconditioning responses and retinal ganglion cell survival after optic nerve crush
2014Co-Authors: Osam Shibeeb, John P M Wood, Robert J Casson, Glyn ChidlowAbstract:Previous research has demonstrated that laser photocoagulation treatment of the monkey retina affords protection against experimental glaucoma-induced retinal ganglion cell (RGC) loss in areas overlying laser spots. The underlying mechanism is unknown, but it is conceivable that the laser acted as a preconditioning stimulus, inducing localised, endogenous production of survival factors. The related purposes of the current study were firstly to examine whether preconditioning pathways are activated by either a conventional Photocoagulator (CW) laser or a photoreceptor-sparing, short-pulse duration (2RT) laser in the rat retina, and secondly, to examine whether such preconditioning with either laser improves RGC survival after optic nerve (ON) crush. Pigmented rats were randomly assigned to one of three groups: sham, CW, 2RT. For the preconditioning study, laser spots were applied randomly to each retina in the posterior hemisphere of the eye taking care to avoid major blood vessels. Animals were killed at 6 h, 1d, and 7d after laser treatment, then analysed by qPCR, immunohistochemistry or Western immunoblotting. For the neuroprotection study, laser spots were administered to the mid-central retina of the right eye. The left eye served as a control. In two experiments, rats were lasered either 24 h or 7 days before ON crush, then killed a further 7 days later. Wholemount retinas were prepared and double labelling immunofluorescence performed. Nestin labelling allowed visualization of laser spots. Brn3a labelling identified viable RGCs. Photomicrographs of Brn3a labelling were taken in areas overlying nestin-positive laser spots. Quantification of Brn3a RGCs was then performed. Both the CW and 2RT lasers induced local glial cell activation. Moreover, both lasers induced localized upregulations of a number of well-documented (CNTF, FGF-2 Hsp27, pAKT) or putative (cFOS, ATF-3, IL-6) RGC survival factors. However, neither laser caused sustained increases in other factors associated with neuronal preconditioning, such as BDNF, Hsp70, IGF-1, bcl-2, and nitric oxide synthase. As regards neuroprotection, analysis of the data revealed that ON crush resulted in the loss of approximately 70% of Brn3a-labelled RGCs after 1 week. Neither the CW nor the 2RT laser augmented Brn3a-positive RGC survival in areas overlying and neighbouring laser spots. This was the case irrespective of whether lasering occurred 1 or 7 days before the ON crush. Our results showed that the CW and 2RT lasers both stimulated de novo synthesis of certain genes that are well-known RGC survival factors and/or that have been implicated in preconditioning-induced neuroprotection studies. Despite these findings, neither laser augmented survival of RGCs when delivered prior to ON crush.
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glial cell and inflammatory responses to retinal laser treatment comparison of a conventional Photocoagulator and a novel 3 nanosecond pulse laser
2013Co-Authors: Glyn Chidlow, Malcolm Plunkett, Osam Shibeeb, Robert J Casson, John P M WoodAbstract:Purpose Retinal laser photocoagulation represents a major treatment strategy for the management of diabetic macular edema (DME). However, the thermal nature of this procedure defines that collateral tissue injury result, meaning that it cannot be used near the fovea centralis. We studied inflammatory and glial responses resulting from treatment of rats with a conventional laser and with a novel short-duration, nonthermal laser (retinal regeneration therapy [2RT]) at clinically relevant energy levels. Methods Pigmented Dark Agouti rats were treated with either a conventional thermal continuous wave (CW; 532-nm, 100-ms pulse duration) or a short-pulse (2RT; 532-nm, Q-switched, 3-ns pulse) laser. Settings were at visible threshold for the CW laser (12.7 J/cm(2)/pulse) and at supra- and subvisible thresholds for the 2RT laser ("high," 2RT-H, 163 mJ/cm(2)/pulse; "low," 2RT-L, 109 mJ/cm(2)/pulse). Rats were killed at various subsequent time points. Samples were processed for histology, immunohistochemistry, RT-PCR, and Western blotting. Results The CW laser caused outer retinal lesions that were associated with photoreceptor death, astrocyte and Muller cell activation, and infiltration of macrophages and neutrophils. Furthermore, inflammatory cytokines, heat shock proteins, endogenous trophic factors, and matrix metalloproteinases were induced. In comparison, all of these changes were drastically attenuated when the 2RT laser was used, particularly at the subthreshold setting. Conclusions The conventional laser produced marked retinal damage and cellular responses consistent with an inflammatory response to thermal injury. In contrast, the 2RT laser produced negligible retinal damage and cellular responses at clinically relevant settings. These results may have important implications for the treatment of retinal disease.
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retinal damage profiles and neuronal effects of laser treatment comparison of a conventional Photocoagulator and a novel 3 nanosecond pulse laser
2013Co-Authors: John P M Wood, Osam Shibeeb, Malcolm Plunkett, Robert J Casson, Glyn ChidlowAbstract:PURPOSE: To determine detailed effects to retinal cells and, in particular, neurons following laser photocoagulation using a conventional 532 nm Nd:YAG continuous wave (CW) laser. Furthermore, to determine whether a novel 3 ns pulse laser (retinal regeneration therapy; 2RT) could specifically ablate retinal pigment epithelium (RPE) cells without causing collateral damage to other retinal cells. METHODS: Adult Dark Agouti (DA) rats were separated into four groups: control, CW laser (12.7 J/cm(2)/pulse, 100 ms pulse duration), or 3 ns pulse 2RT laser at one of two energy settings ("High," 2RT-H, 163 mJ/cm(2)/pulse; "Low," 2RT-L, 109 mJ/cm(2)/pulse). Animals were treated and killed after 6 hours to 7 days, and retina/RPE was analyzed by histologic assessment, Western blot, polymerase chain reaction, and immunohistochemistry. RESULTS: Both lasers caused focal loss of RPE cells with no destruction of Bruch's membrane; RPE cells were present at lesion sites again within 7 days of treatments. CW and 2RT-H treatments caused extensive and moderate damage, respectively, to the outer retina. There were no obvious effects to horizontal, amacrine, or ganglion cells, as defined by immunolabeling, but an activation of PKCα within bipolar cells was noted. There was little discernible damage to any cells other than the RPE with the 2RT-L treatment. CONCLUSIONS: Conventional laser photocoagulation caused death of RPE cells with associated widespread damage to the outer retina but little influence on the inner retina. The novel 3 ns 2RT laser, however, was able to selectively kill RPE cells without causing collateral damage to photoreceptors. Potential benefits of this laser for clinical treatment of diabetic macular edema are discussed.
Osam Shibeeb - One of the best experts on this subject based on the ideXlab platform.
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effects of a conventional Photocoagulator and a 3 ns pulse laser on preconditioning responses and retinal ganglion cell survival after optic nerve crush
2014Co-Authors: Osam Shibeeb, John P M Wood, Robert J Casson, Glyn ChidlowAbstract:Previous research has demonstrated that laser photocoagulation treatment of the monkey retina affords protection against experimental glaucoma-induced retinal ganglion cell (RGC) loss in areas overlying laser spots. The underlying mechanism is unknown, but it is conceivable that the laser acted as a preconditioning stimulus, inducing localised, endogenous production of survival factors. The related purposes of the current study were firstly to examine whether preconditioning pathways are activated by either a conventional Photocoagulator (CW) laser or a photoreceptor-sparing, short-pulse duration (2RT) laser in the rat retina, and secondly, to examine whether such preconditioning with either laser improves RGC survival after optic nerve (ON) crush. Pigmented rats were randomly assigned to one of three groups: sham, CW, 2RT. For the preconditioning study, laser spots were applied randomly to each retina in the posterior hemisphere of the eye taking care to avoid major blood vessels. Animals were killed at 6 h, 1d, and 7d after laser treatment, then analysed by qPCR, immunohistochemistry or Western immunoblotting. For the neuroprotection study, laser spots were administered to the mid-central retina of the right eye. The left eye served as a control. In two experiments, rats were lasered either 24 h or 7 days before ON crush, then killed a further 7 days later. Wholemount retinas were prepared and double labelling immunofluorescence performed. Nestin labelling allowed visualization of laser spots. Brn3a labelling identified viable RGCs. Photomicrographs of Brn3a labelling were taken in areas overlying nestin-positive laser spots. Quantification of Brn3a RGCs was then performed. Both the CW and 2RT lasers induced local glial cell activation. Moreover, both lasers induced localized upregulations of a number of well-documented (CNTF, FGF-2 Hsp27, pAKT) or putative (cFOS, ATF-3, IL-6) RGC survival factors. However, neither laser caused sustained increases in other factors associated with neuronal preconditioning, such as BDNF, Hsp70, IGF-1, bcl-2, and nitric oxide synthase. As regards neuroprotection, analysis of the data revealed that ON crush resulted in the loss of approximately 70% of Brn3a-labelled RGCs after 1 week. Neither the CW nor the 2RT laser augmented Brn3a-positive RGC survival in areas overlying and neighbouring laser spots. This was the case irrespective of whether lasering occurred 1 or 7 days before the ON crush. Our results showed that the CW and 2RT lasers both stimulated de novo synthesis of certain genes that are well-known RGC survival factors and/or that have been implicated in preconditioning-induced neuroprotection studies. Despite these findings, neither laser augmented survival of RGCs when delivered prior to ON crush.
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glial cell and inflammatory responses to retinal laser treatment comparison of a conventional Photocoagulator and a novel 3 nanosecond pulse laser
2013Co-Authors: Glyn Chidlow, Malcolm Plunkett, Osam Shibeeb, Robert J Casson, John P M WoodAbstract:Purpose Retinal laser photocoagulation represents a major treatment strategy for the management of diabetic macular edema (DME). However, the thermal nature of this procedure defines that collateral tissue injury result, meaning that it cannot be used near the fovea centralis. We studied inflammatory and glial responses resulting from treatment of rats with a conventional laser and with a novel short-duration, nonthermal laser (retinal regeneration therapy [2RT]) at clinically relevant energy levels. Methods Pigmented Dark Agouti rats were treated with either a conventional thermal continuous wave (CW; 532-nm, 100-ms pulse duration) or a short-pulse (2RT; 532-nm, Q-switched, 3-ns pulse) laser. Settings were at visible threshold for the CW laser (12.7 J/cm(2)/pulse) and at supra- and subvisible thresholds for the 2RT laser ("high," 2RT-H, 163 mJ/cm(2)/pulse; "low," 2RT-L, 109 mJ/cm(2)/pulse). Rats were killed at various subsequent time points. Samples were processed for histology, immunohistochemistry, RT-PCR, and Western blotting. Results The CW laser caused outer retinal lesions that were associated with photoreceptor death, astrocyte and Muller cell activation, and infiltration of macrophages and neutrophils. Furthermore, inflammatory cytokines, heat shock proteins, endogenous trophic factors, and matrix metalloproteinases were induced. In comparison, all of these changes were drastically attenuated when the 2RT laser was used, particularly at the subthreshold setting. Conclusions The conventional laser produced marked retinal damage and cellular responses consistent with an inflammatory response to thermal injury. In contrast, the 2RT laser produced negligible retinal damage and cellular responses at clinically relevant settings. These results may have important implications for the treatment of retinal disease.
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retinal damage profiles and neuronal effects of laser treatment comparison of a conventional Photocoagulator and a novel 3 nanosecond pulse laser
2013Co-Authors: John P M Wood, Osam Shibeeb, Malcolm Plunkett, Robert J Casson, Glyn ChidlowAbstract:PURPOSE: To determine detailed effects to retinal cells and, in particular, neurons following laser photocoagulation using a conventional 532 nm Nd:YAG continuous wave (CW) laser. Furthermore, to determine whether a novel 3 ns pulse laser (retinal regeneration therapy; 2RT) could specifically ablate retinal pigment epithelium (RPE) cells without causing collateral damage to other retinal cells. METHODS: Adult Dark Agouti (DA) rats were separated into four groups: control, CW laser (12.7 J/cm(2)/pulse, 100 ms pulse duration), or 3 ns pulse 2RT laser at one of two energy settings ("High," 2RT-H, 163 mJ/cm(2)/pulse; "Low," 2RT-L, 109 mJ/cm(2)/pulse). Animals were treated and killed after 6 hours to 7 days, and retina/RPE was analyzed by histologic assessment, Western blot, polymerase chain reaction, and immunohistochemistry. RESULTS: Both lasers caused focal loss of RPE cells with no destruction of Bruch's membrane; RPE cells were present at lesion sites again within 7 days of treatments. CW and 2RT-H treatments caused extensive and moderate damage, respectively, to the outer retina. There were no obvious effects to horizontal, amacrine, or ganglion cells, as defined by immunolabeling, but an activation of PKCα within bipolar cells was noted. There was little discernible damage to any cells other than the RPE with the 2RT-L treatment. CONCLUSIONS: Conventional laser photocoagulation caused death of RPE cells with associated widespread damage to the outer retina but little influence on the inner retina. The novel 3 ns 2RT laser, however, was able to selectively kill RPE cells without causing collateral damage to photoreceptors. Potential benefits of this laser for clinical treatment of diabetic macular edema are discussed.
Robert J Casson - One of the best experts on this subject based on the ideXlab platform.
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effects of a conventional Photocoagulator and a 3 ns pulse laser on preconditioning responses and retinal ganglion cell survival after optic nerve crush
2014Co-Authors: Osam Shibeeb, John P M Wood, Robert J Casson, Glyn ChidlowAbstract:Previous research has demonstrated that laser photocoagulation treatment of the monkey retina affords protection against experimental glaucoma-induced retinal ganglion cell (RGC) loss in areas overlying laser spots. The underlying mechanism is unknown, but it is conceivable that the laser acted as a preconditioning stimulus, inducing localised, endogenous production of survival factors. The related purposes of the current study were firstly to examine whether preconditioning pathways are activated by either a conventional Photocoagulator (CW) laser or a photoreceptor-sparing, short-pulse duration (2RT) laser in the rat retina, and secondly, to examine whether such preconditioning with either laser improves RGC survival after optic nerve (ON) crush. Pigmented rats were randomly assigned to one of three groups: sham, CW, 2RT. For the preconditioning study, laser spots were applied randomly to each retina in the posterior hemisphere of the eye taking care to avoid major blood vessels. Animals were killed at 6 h, 1d, and 7d after laser treatment, then analysed by qPCR, immunohistochemistry or Western immunoblotting. For the neuroprotection study, laser spots were administered to the mid-central retina of the right eye. The left eye served as a control. In two experiments, rats were lasered either 24 h or 7 days before ON crush, then killed a further 7 days later. Wholemount retinas were prepared and double labelling immunofluorescence performed. Nestin labelling allowed visualization of laser spots. Brn3a labelling identified viable RGCs. Photomicrographs of Brn3a labelling were taken in areas overlying nestin-positive laser spots. Quantification of Brn3a RGCs was then performed. Both the CW and 2RT lasers induced local glial cell activation. Moreover, both lasers induced localized upregulations of a number of well-documented (CNTF, FGF-2 Hsp27, pAKT) or putative (cFOS, ATF-3, IL-6) RGC survival factors. However, neither laser caused sustained increases in other factors associated with neuronal preconditioning, such as BDNF, Hsp70, IGF-1, bcl-2, and nitric oxide synthase. As regards neuroprotection, analysis of the data revealed that ON crush resulted in the loss of approximately 70% of Brn3a-labelled RGCs after 1 week. Neither the CW nor the 2RT laser augmented Brn3a-positive RGC survival in areas overlying and neighbouring laser spots. This was the case irrespective of whether lasering occurred 1 or 7 days before the ON crush. Our results showed that the CW and 2RT lasers both stimulated de novo synthesis of certain genes that are well-known RGC survival factors and/or that have been implicated in preconditioning-induced neuroprotection studies. Despite these findings, neither laser augmented survival of RGCs when delivered prior to ON crush.
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glial cell and inflammatory responses to retinal laser treatment comparison of a conventional Photocoagulator and a novel 3 nanosecond pulse laser
2013Co-Authors: Glyn Chidlow, Malcolm Plunkett, Osam Shibeeb, Robert J Casson, John P M WoodAbstract:Purpose Retinal laser photocoagulation represents a major treatment strategy for the management of diabetic macular edema (DME). However, the thermal nature of this procedure defines that collateral tissue injury result, meaning that it cannot be used near the fovea centralis. We studied inflammatory and glial responses resulting from treatment of rats with a conventional laser and with a novel short-duration, nonthermal laser (retinal regeneration therapy [2RT]) at clinically relevant energy levels. Methods Pigmented Dark Agouti rats were treated with either a conventional thermal continuous wave (CW; 532-nm, 100-ms pulse duration) or a short-pulse (2RT; 532-nm, Q-switched, 3-ns pulse) laser. Settings were at visible threshold for the CW laser (12.7 J/cm(2)/pulse) and at supra- and subvisible thresholds for the 2RT laser ("high," 2RT-H, 163 mJ/cm(2)/pulse; "low," 2RT-L, 109 mJ/cm(2)/pulse). Rats were killed at various subsequent time points. Samples were processed for histology, immunohistochemistry, RT-PCR, and Western blotting. Results The CW laser caused outer retinal lesions that were associated with photoreceptor death, astrocyte and Muller cell activation, and infiltration of macrophages and neutrophils. Furthermore, inflammatory cytokines, heat shock proteins, endogenous trophic factors, and matrix metalloproteinases were induced. In comparison, all of these changes were drastically attenuated when the 2RT laser was used, particularly at the subthreshold setting. Conclusions The conventional laser produced marked retinal damage and cellular responses consistent with an inflammatory response to thermal injury. In contrast, the 2RT laser produced negligible retinal damage and cellular responses at clinically relevant settings. These results may have important implications for the treatment of retinal disease.
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retinal damage profiles and neuronal effects of laser treatment comparison of a conventional Photocoagulator and a novel 3 nanosecond pulse laser
2013Co-Authors: John P M Wood, Osam Shibeeb, Malcolm Plunkett, Robert J Casson, Glyn ChidlowAbstract:PURPOSE: To determine detailed effects to retinal cells and, in particular, neurons following laser photocoagulation using a conventional 532 nm Nd:YAG continuous wave (CW) laser. Furthermore, to determine whether a novel 3 ns pulse laser (retinal regeneration therapy; 2RT) could specifically ablate retinal pigment epithelium (RPE) cells without causing collateral damage to other retinal cells. METHODS: Adult Dark Agouti (DA) rats were separated into four groups: control, CW laser (12.7 J/cm(2)/pulse, 100 ms pulse duration), or 3 ns pulse 2RT laser at one of two energy settings ("High," 2RT-H, 163 mJ/cm(2)/pulse; "Low," 2RT-L, 109 mJ/cm(2)/pulse). Animals were treated and killed after 6 hours to 7 days, and retina/RPE was analyzed by histologic assessment, Western blot, polymerase chain reaction, and immunohistochemistry. RESULTS: Both lasers caused focal loss of RPE cells with no destruction of Bruch's membrane; RPE cells were present at lesion sites again within 7 days of treatments. CW and 2RT-H treatments caused extensive and moderate damage, respectively, to the outer retina. There were no obvious effects to horizontal, amacrine, or ganglion cells, as defined by immunolabeling, but an activation of PKCα within bipolar cells was noted. There was little discernible damage to any cells other than the RPE with the 2RT-L treatment. CONCLUSIONS: Conventional laser photocoagulation caused death of RPE cells with associated widespread damage to the outer retina but little influence on the inner retina. The novel 3 ns 2RT laser, however, was able to selectively kill RPE cells without causing collateral damage to photoreceptors. Potential benefits of this laser for clinical treatment of diabetic macular edema are discussed.
Malcolm Plunkett - One of the best experts on this subject based on the ideXlab platform.
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glial cell and inflammatory responses to retinal laser treatment comparison of a conventional Photocoagulator and a novel 3 nanosecond pulse laser
2013Co-Authors: Glyn Chidlow, Malcolm Plunkett, Osam Shibeeb, Robert J Casson, John P M WoodAbstract:Purpose Retinal laser photocoagulation represents a major treatment strategy for the management of diabetic macular edema (DME). However, the thermal nature of this procedure defines that collateral tissue injury result, meaning that it cannot be used near the fovea centralis. We studied inflammatory and glial responses resulting from treatment of rats with a conventional laser and with a novel short-duration, nonthermal laser (retinal regeneration therapy [2RT]) at clinically relevant energy levels. Methods Pigmented Dark Agouti rats were treated with either a conventional thermal continuous wave (CW; 532-nm, 100-ms pulse duration) or a short-pulse (2RT; 532-nm, Q-switched, 3-ns pulse) laser. Settings were at visible threshold for the CW laser (12.7 J/cm(2)/pulse) and at supra- and subvisible thresholds for the 2RT laser ("high," 2RT-H, 163 mJ/cm(2)/pulse; "low," 2RT-L, 109 mJ/cm(2)/pulse). Rats were killed at various subsequent time points. Samples were processed for histology, immunohistochemistry, RT-PCR, and Western blotting. Results The CW laser caused outer retinal lesions that were associated with photoreceptor death, astrocyte and Muller cell activation, and infiltration of macrophages and neutrophils. Furthermore, inflammatory cytokines, heat shock proteins, endogenous trophic factors, and matrix metalloproteinases were induced. In comparison, all of these changes were drastically attenuated when the 2RT laser was used, particularly at the subthreshold setting. Conclusions The conventional laser produced marked retinal damage and cellular responses consistent with an inflammatory response to thermal injury. In contrast, the 2RT laser produced negligible retinal damage and cellular responses at clinically relevant settings. These results may have important implications for the treatment of retinal disease.
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retinal damage profiles and neuronal effects of laser treatment comparison of a conventional Photocoagulator and a novel 3 nanosecond pulse laser
2013Co-Authors: John P M Wood, Osam Shibeeb, Malcolm Plunkett, Robert J Casson, Glyn ChidlowAbstract:PURPOSE: To determine detailed effects to retinal cells and, in particular, neurons following laser photocoagulation using a conventional 532 nm Nd:YAG continuous wave (CW) laser. Furthermore, to determine whether a novel 3 ns pulse laser (retinal regeneration therapy; 2RT) could specifically ablate retinal pigment epithelium (RPE) cells without causing collateral damage to other retinal cells. METHODS: Adult Dark Agouti (DA) rats were separated into four groups: control, CW laser (12.7 J/cm(2)/pulse, 100 ms pulse duration), or 3 ns pulse 2RT laser at one of two energy settings ("High," 2RT-H, 163 mJ/cm(2)/pulse; "Low," 2RT-L, 109 mJ/cm(2)/pulse). Animals were treated and killed after 6 hours to 7 days, and retina/RPE was analyzed by histologic assessment, Western blot, polymerase chain reaction, and immunohistochemistry. RESULTS: Both lasers caused focal loss of RPE cells with no destruction of Bruch's membrane; RPE cells were present at lesion sites again within 7 days of treatments. CW and 2RT-H treatments caused extensive and moderate damage, respectively, to the outer retina. There were no obvious effects to horizontal, amacrine, or ganglion cells, as defined by immunolabeling, but an activation of PKCα within bipolar cells was noted. There was little discernible damage to any cells other than the RPE with the 2RT-L treatment. CONCLUSIONS: Conventional laser photocoagulation caused death of RPE cells with associated widespread damage to the outer retina but little influence on the inner retina. The novel 3 ns 2RT laser, however, was able to selectively kill RPE cells without causing collateral damage to photoreceptors. Potential benefits of this laser for clinical treatment of diabetic macular edema are discussed.