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Biomolecules ; 14(5)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38785932

RESUMO

Augmenting the natural melanocortin pathway in mouse eyes with uveitis or diabetes protects the retinas from degeneration. The retinal cells are protected from oxidative and apoptotic signals of death. Therefore, we investigated the effects of a therapeutic application of the melanocortin alpha-melanocyte-stimulating hormone (α-MSH) on an ischemia and reperfusion (I/R) model of retinal degenerative disease. Eyes were subjected to an I/R procedure and were treated with α-MSH. Retinal sections were histopathologically scored. Also, the retinal sections were immunostained for viable ganglion cells, activated Muller cells, microglial cells, and apoptosis. The I/R caused retinal deformation and ganglion cell loss that was significantly reduced in I/R eyes treated with α-MSH. While α-MSH treatment marginally reduced the number of GFAP-positive Muller cells, it significantly suppressed the density of Iba1-positive microglial cells in the I/R retinas. Within one hour after I/R, there was apoptosis in the ganglion cell layer, and by 48 h, there was apoptosis in all layers of the neuroretina. The α-MSH treatment significantly reduced and delayed the onset of apoptosis in the retinas of I/R eyes. The results demonstrate that therapeutically augmenting the melanocortin pathways preserves retinal structure and cell survival in eyes with progressive neuroretinal degenerative disease.


Assuntos
Apoptose , Homeostase , Traumatismo por Reperfusão , Retina , Células Ganglionares da Retina , alfa-MSH , Animais , alfa-MSH/farmacologia , alfa-MSH/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Camundongos , Apoptose/efeitos dos fármacos , Retina/metabolismo , Retina/efeitos dos fármacos , Retina/patologia , Homeostase/efeitos dos fármacos , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/efeitos dos fármacos , Masculino , Células Ependimogliais/metabolismo , Células Ependimogliais/efeitos dos fármacos , Células Ependimogliais/patologia , Modelos Animais de Doenças , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Degeneração Retiniana/tratamento farmacológico
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