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DORFMAN Damian

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Título:

Superior cervical gangliectomy induces geographic atrophy in mice

Autor/es:

DORFMAN, DAMIÁN; DIEGUEZ, HERNÁN H; GONZÁLEZ FLEITAS, MARÍA F; ARANDA, MARCOS L; SANDE PABLO H; ROMEO, HORACIO E; ROSENSTEIN, RUTH E

Lugar:

Baltimore

Reunión:

Congreso; ARVO Annual Meeting 2017; 2017

Resumen:

Purpose:Age related macular degeneration (AMD) is a maincause of irreversible blindness. AMD is classified in two forms: wet orneovascular, and dry or geographic atrophy (GA). GA is characterized byhypopigmentation of the retinal pigment epithelium (RPE) and photoreceptor (FR)loss in a localized area of the retina. Alterations in choroid blood flow havebeen related in the pathogenesis of GA. Sympathetic terminals from the superiorcervical sympathetic ganglion (SCG) innervate choroid vessels and modulatetheir flux. Superior cervical gangliectomy (SCGx) induces complete and irreversibleipsilateral choroid denervation. The aim of this work was to analyze the effectof SCGx on the retina/RPE in mice.Methods:Unilateral SCGx was induced in adult male C57BL/6Jmice, while the contralateral side was submitted to a sham procedure, withoutexcision of SCG (control). At 4, 6, and 10 weeks after SCGx, retinal function(electroretinography, ERG), RPE melanin content (histology), all-trans retinylester binding protein (RPE65) levels (immunohistochemistry), retinal histology(toluidine blue), FR and RPE apoptosis (TUNEL assay), and choroid, Bruch′smembrane, RPE and FR ultrastructure (electron microscopy) were assessed.Results:At 4 weeks post-SCGx, a significant decrease inscotopic ERG a-wave amplitude, which was even higher after 6 and 10 weeks ofSCGx was found, without changes in ERG b-wave or oscillatory potentials. SCGxinduced a loss of the temporal (but not nasal) RPE melanin content and RPE65levels at 4 weeks post-SCGx, which was greater at 6 and 10 weeks post-SCGx. At10 weeks after SCGx, TUNEL(+) cells were found in the temporal retinal outernuclear layer and temporal RPE, while no TUNEL(+) cells were observed in thenasal side at all time points. After 4 weeks, SGCx induced a significantincrease in choriocapillaris thickness both in the nasal and temporal side,which persisted after 10 weeks of surgery, while no changes in total choroidthickness was found neither in the nasal nor in the temporal side in allexperimental groups. After 6 and 10 weeks of SGCx, we found a significant increaseBruch′s membrane thickness and RPE and FR outer segment morphologicalalterations in the temporal (but not nasal) side.Conclusions:These results show that SCGx induced alterations whichare compatible with GA in the retina of the mice.

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