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Protective effect of alpha-melanocyte-stimulating hormone (α-MSH) on the recovery of ischemia/reperfusion (I/R)-induced retinal damage in a rat model.

Varga B, Gesztelyi R, Bombicz M, Haines D, Szabo AM, Kemeny-Beke A, Antal M, Vecsernyes M, Juhasz B, Tosaki A - J. Mol. Neurosci. (2013)

Bottom Line: The observation that post-ischemic treatment with α-MSH exhibits therapeutic efficacy in the same range as pre-ischemic treatment, is a novel result.This outcome suggests a highly conserved protective role for α-MSH as a major stress response mechanism--and offers the possibility for development of novel therapeutic strategies utilizing this hormone, in particular in treatment of conditions resulting from I/R injury, such as deterioration of retinal microcirculation.The merit of the study lies in the fact that I/R injury contribute significantly to the severity of retinopathies.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Pharmacy, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary. varga.balazs@pharm.unideb.hu

ABSTRACT
The present study demonstrates capacity of α-MSH to augment recovery from ischemia/reperfusion (I/R)-induced retinal damage in vivo and correlation of its protective effects with expression of heme oxygenase-1 (HO-1). Used techniques include ocular ischemia and reperfusion, electroretinography, histology, electron microscopy, and molecular-biological techniques. The results demonstrate the α-MSH-mediated inhibition of I/R-induced functional deterioration of the retina. Outcomes suggest that the protective effects of α-MSH occur mainly through HO-1-dependent pathways but HO-1-independent mechanisms may also contribute to protection. The observation that post-ischemic treatment with α-MSH exhibits therapeutic efficacy in the same range as pre-ischemic treatment, is a novel result. This outcome suggests a highly conserved protective role for α-MSH as a major stress response mechanism--and offers the possibility for development of novel therapeutic strategies utilizing this hormone, in particular in treatment of conditions resulting from I/R injury, such as deterioration of retinal microcirculation. The merit of the study lies in the fact that I/R injury contribute significantly to the severity of retinopathies. However, currently there are no evidence-based treatments for retinal I/R injury available for clinical use. Our finding suggests that α-MSH may have a very wide range of uses in the prevention of I/R-mediated pathologies.

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EM studies (group I-b). a–c Mitochondria in I/R-injured inner retinal cells from rats not treated with α-MSH. These images demonstrate disintegration of the mitochondria due to formation of interior vacuoles (arrows). Mitochondria in I/R-injured inner retinal cells from animals treated with 500 μg/kg α-MSH are shown in (d–g). No vacuolization is seen here
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Fig4: EM studies (group I-b). a–c Mitochondria in I/R-injured inner retinal cells from rats not treated with α-MSH. These images demonstrate disintegration of the mitochondria due to formation of interior vacuoles (arrows). Mitochondria in I/R-injured inner retinal cells from animals treated with 500 μg/kg α-MSH are shown in (d–g). No vacuolization is seen here

Mentions: EM ultrastructure of retinal pigment cells and photoreceptors revealed no apparent morphological changes in cells in the outer retinal layers following I/R injury (data not shown). However, I/R-mediated damage to mitochondria of inner retinal cells was clearly observed. Figure 4a through c shows damaged mitochondria in inner retinal cells of I/R-injured retinal tissue from control animals. These images demonstrate disintegration of the mitochondria due to formation of interior vacuoles. By contrast, inner retinal cell mitochondria from I/R-injured retinas taken from animals treated with 500 μg/kg α-MSH appeared intact with no vacuolization (Fig. 4d through g). Significant differences between control and treated non-I/R ultrastructure were not observed (data not shown).Fig. 4


Protective effect of alpha-melanocyte-stimulating hormone (α-MSH) on the recovery of ischemia/reperfusion (I/R)-induced retinal damage in a rat model.

Varga B, Gesztelyi R, Bombicz M, Haines D, Szabo AM, Kemeny-Beke A, Antal M, Vecsernyes M, Juhasz B, Tosaki A - J. Mol. Neurosci. (2013)

EM studies (group I-b). a–c Mitochondria in I/R-injured inner retinal cells from rats not treated with α-MSH. These images demonstrate disintegration of the mitochondria due to formation of interior vacuoles (arrows). Mitochondria in I/R-injured inner retinal cells from animals treated with 500 μg/kg α-MSH are shown in (d–g). No vacuolization is seen here
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675276&req=5

Fig4: EM studies (group I-b). a–c Mitochondria in I/R-injured inner retinal cells from rats not treated with α-MSH. These images demonstrate disintegration of the mitochondria due to formation of interior vacuoles (arrows). Mitochondria in I/R-injured inner retinal cells from animals treated with 500 μg/kg α-MSH are shown in (d–g). No vacuolization is seen here
Mentions: EM ultrastructure of retinal pigment cells and photoreceptors revealed no apparent morphological changes in cells in the outer retinal layers following I/R injury (data not shown). However, I/R-mediated damage to mitochondria of inner retinal cells was clearly observed. Figure 4a through c shows damaged mitochondria in inner retinal cells of I/R-injured retinal tissue from control animals. These images demonstrate disintegration of the mitochondria due to formation of interior vacuoles. By contrast, inner retinal cell mitochondria from I/R-injured retinas taken from animals treated with 500 μg/kg α-MSH appeared intact with no vacuolization (Fig. 4d through g). Significant differences between control and treated non-I/R ultrastructure were not observed (data not shown).Fig. 4

Bottom Line: The observation that post-ischemic treatment with α-MSH exhibits therapeutic efficacy in the same range as pre-ischemic treatment, is a novel result.This outcome suggests a highly conserved protective role for α-MSH as a major stress response mechanism--and offers the possibility for development of novel therapeutic strategies utilizing this hormone, in particular in treatment of conditions resulting from I/R injury, such as deterioration of retinal microcirculation.The merit of the study lies in the fact that I/R injury contribute significantly to the severity of retinopathies.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Pharmacy, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary. varga.balazs@pharm.unideb.hu

ABSTRACT
The present study demonstrates capacity of α-MSH to augment recovery from ischemia/reperfusion (I/R)-induced retinal damage in vivo and correlation of its protective effects with expression of heme oxygenase-1 (HO-1). Used techniques include ocular ischemia and reperfusion, electroretinography, histology, electron microscopy, and molecular-biological techniques. The results demonstrate the α-MSH-mediated inhibition of I/R-induced functional deterioration of the retina. Outcomes suggest that the protective effects of α-MSH occur mainly through HO-1-dependent pathways but HO-1-independent mechanisms may also contribute to protection. The observation that post-ischemic treatment with α-MSH exhibits therapeutic efficacy in the same range as pre-ischemic treatment, is a novel result. This outcome suggests a highly conserved protective role for α-MSH as a major stress response mechanism--and offers the possibility for development of novel therapeutic strategies utilizing this hormone, in particular in treatment of conditions resulting from I/R injury, such as deterioration of retinal microcirculation. The merit of the study lies in the fact that I/R injury contribute significantly to the severity of retinopathies. However, currently there are no evidence-based treatments for retinal I/R injury available for clinical use. Our finding suggests that α-MSH may have a very wide range of uses in the prevention of I/R-mediated pathologies.

Show MeSH
Related in: MedlinePlus