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Combining neuroprotectants in a model of retinal degeneration: no additive benefit.

Di Marco F, Di Paolo M, Romeo S, Colecchi L, Fiorani L, Spana S, Stone J, Bisti S - PLoS ONE (2014)

Bottom Line: Results confirmed the neuroprotective potential of each used separately, but gave no evidence that their effects are additive.Detailed analysis suggests that there is actually a negative interaction between PBM and saffron when given simultaneously, with a consequent reduction of the neuroprotection.Specific testing will be required to understand the mechanisms involved and to establish whether there is clinical potential in combining neuroprotectants, to improve the quality of life of people affected by retinal pathology, such as age-related macular degeneration, the major cause of blindness and visual impairment in older adults.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Applied Clinical Science, University of L'Aquila, L'Aquila, Italy.

ABSTRACT
The central nervous system undergoing degeneration can be stabilized, and in some models can be restored to function, by neuroprotective treatments. Photobiomodulation (PBM) and dietary saffron are distinctive as neuroprotectants in that they upregulate protective mechanisms, without causing measurable tissue damage. This study reports a first attempt to combine the actions of PBM and saffron. Our working hypothesis was that the actions of PBM and saffron in protecting retinal photoreceptors, in a rat light damage model, would be additive. Results confirmed the neuroprotective potential of each used separately, but gave no evidence that their effects are additive. Detailed analysis suggests that there is actually a negative interaction between PBM and saffron when given simultaneously, with a consequent reduction of the neuroprotection. Specific testing will be required to understand the mechanisms involved and to establish whether there is clinical potential in combining neuroprotectants, to improve the quality of life of people affected by retinal pathology, such as age-related macular degeneration, the major cause of blindness and visual impairment in older adults.

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Impact of single and combined neuroprotectants on GFAP labelling of Müller cells.A–E: Representative GFAP labelling in control (A), light damage (B), 7 d PBM (C), 10 d saffron (D) and combined treatment (E) groups, 1 w after light damage. Light damage induced the up-regulation of GFAP in the radially oriented Müller cells; the protein is visible along the full length of the Müller cells, from the ILM to the OLM. F: Length of the Müller processes expressing GFAP as a function of distance from superior edge in the five experimental groups. The arrow shows the position of the optic disc. Each point shows the mean labelled length; error bars show standard deviations of the mean. G: Mean length of Müller processes expressing GFAP, averaged across superior retina, in: Control (A), Light Damage (B), 7 days PBM (C), 10 days saffron (D) and combined (E) groups. In all treated groups, the length of Müller cells expressing GFAP was less than in the light damage group. The error bars show standard errors of the mean. Statistical significance indicator: (***) p<0.001.
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pone-0100389-g003: Impact of single and combined neuroprotectants on GFAP labelling of Müller cells.A–E: Representative GFAP labelling in control (A), light damage (B), 7 d PBM (C), 10 d saffron (D) and combined treatment (E) groups, 1 w after light damage. Light damage induced the up-regulation of GFAP in the radially oriented Müller cells; the protein is visible along the full length of the Müller cells, from the ILM to the OLM. F: Length of the Müller processes expressing GFAP as a function of distance from superior edge in the five experimental groups. The arrow shows the position of the optic disc. Each point shows the mean labelled length; error bars show standard deviations of the mean. G: Mean length of Müller processes expressing GFAP, averaged across superior retina, in: Control (A), Light Damage (B), 7 days PBM (C), 10 days saffron (D) and combined (E) groups. In all treated groups, the length of Müller cells expressing GFAP was less than in the light damage group. The error bars show standard errors of the mean. Statistical significance indicator: (***) p<0.001.

Mentions: Figure 3 shows GFAP expression in the retina, in the five experimental groups. Without light damage or conditioning, GFAP expression is confined to the astrocytes at the inner surface of the retina (Figure 3A). Light damage induced the upregulation of GFAP in the radially oriented Müller cells; the protein was visible along the full length of the Müller cell (Figure 3B). The length of the Müller cell that expressed GFAP was shortened by 7d conditioning with PBM and by 10d conditioning with saffron, confirming previous study [5] (Figures 3C, D). The length of Müller cells labelled by combined conditioning is shown in Figure 3E.


Combining neuroprotectants in a model of retinal degeneration: no additive benefit.

Di Marco F, Di Paolo M, Romeo S, Colecchi L, Fiorani L, Spana S, Stone J, Bisti S - PLoS ONE (2014)

Impact of single and combined neuroprotectants on GFAP labelling of Müller cells.A–E: Representative GFAP labelling in control (A), light damage (B), 7 d PBM (C), 10 d saffron (D) and combined treatment (E) groups, 1 w after light damage. Light damage induced the up-regulation of GFAP in the radially oriented Müller cells; the protein is visible along the full length of the Müller cells, from the ILM to the OLM. F: Length of the Müller processes expressing GFAP as a function of distance from superior edge in the five experimental groups. The arrow shows the position of the optic disc. Each point shows the mean labelled length; error bars show standard deviations of the mean. G: Mean length of Müller processes expressing GFAP, averaged across superior retina, in: Control (A), Light Damage (B), 7 days PBM (C), 10 days saffron (D) and combined (E) groups. In all treated groups, the length of Müller cells expressing GFAP was less than in the light damage group. The error bars show standard errors of the mean. Statistical significance indicator: (***) p<0.001.
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Related In: Results  -  Collection

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pone-0100389-g003: Impact of single and combined neuroprotectants on GFAP labelling of Müller cells.A–E: Representative GFAP labelling in control (A), light damage (B), 7 d PBM (C), 10 d saffron (D) and combined treatment (E) groups, 1 w after light damage. Light damage induced the up-regulation of GFAP in the radially oriented Müller cells; the protein is visible along the full length of the Müller cells, from the ILM to the OLM. F: Length of the Müller processes expressing GFAP as a function of distance from superior edge in the five experimental groups. The arrow shows the position of the optic disc. Each point shows the mean labelled length; error bars show standard deviations of the mean. G: Mean length of Müller processes expressing GFAP, averaged across superior retina, in: Control (A), Light Damage (B), 7 days PBM (C), 10 days saffron (D) and combined (E) groups. In all treated groups, the length of Müller cells expressing GFAP was less than in the light damage group. The error bars show standard errors of the mean. Statistical significance indicator: (***) p<0.001.
Mentions: Figure 3 shows GFAP expression in the retina, in the five experimental groups. Without light damage or conditioning, GFAP expression is confined to the astrocytes at the inner surface of the retina (Figure 3A). Light damage induced the upregulation of GFAP in the radially oriented Müller cells; the protein was visible along the full length of the Müller cell (Figure 3B). The length of the Müller cell that expressed GFAP was shortened by 7d conditioning with PBM and by 10d conditioning with saffron, confirming previous study [5] (Figures 3C, D). The length of Müller cells labelled by combined conditioning is shown in Figure 3E.

Bottom Line: Results confirmed the neuroprotective potential of each used separately, but gave no evidence that their effects are additive.Detailed analysis suggests that there is actually a negative interaction between PBM and saffron when given simultaneously, with a consequent reduction of the neuroprotection.Specific testing will be required to understand the mechanisms involved and to establish whether there is clinical potential in combining neuroprotectants, to improve the quality of life of people affected by retinal pathology, such as age-related macular degeneration, the major cause of blindness and visual impairment in older adults.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Applied Clinical Science, University of L'Aquila, L'Aquila, Italy.

ABSTRACT
The central nervous system undergoing degeneration can be stabilized, and in some models can be restored to function, by neuroprotective treatments. Photobiomodulation (PBM) and dietary saffron are distinctive as neuroprotectants in that they upregulate protective mechanisms, without causing measurable tissue damage. This study reports a first attempt to combine the actions of PBM and saffron. Our working hypothesis was that the actions of PBM and saffron in protecting retinal photoreceptors, in a rat light damage model, would be additive. Results confirmed the neuroprotective potential of each used separately, but gave no evidence that their effects are additive. Detailed analysis suggests that there is actually a negative interaction between PBM and saffron when given simultaneously, with a consequent reduction of the neuroprotection. Specific testing will be required to understand the mechanisms involved and to establish whether there is clinical potential in combining neuroprotectants, to improve the quality of life of people affected by retinal pathology, such as age-related macular degeneration, the major cause of blindness and visual impairment in older adults.

Show MeSH
Related in: MedlinePlus