SUPERIOR CERVICAL GANGLIONECTOMY INDUCES GEOGRAPHIC ATROPHY IN MICES

DORFMAN, D., DIEGUEZ, H., GONZALEZ FLEITAS, F., ARANDA, M., SANDE, P., ROSENSTEIN, R.; ROMEO, HORACIO E.

Baltimore

Congreso; 2017 ARVO Annual Meeting; 2017

ARVO

Purpose : Age related maculardegeneration (AMD) is a main cause of irreversible blindness. AMD is classifiedin two forms: wet or neovascular, and dry or geographic atrophy (GA). GA ischaracterized by hypopigmentation of the retinal pigment epithelium (RPE) andphotoreceptor (FR) loss in a localized area of the retina. Alterations inchoroid blood flow have been related in the pathogenesis of GA. Sympatheticterminals from the superior cervical sympathetic ganglion (SCG) innervatechoroid vessels and modulate their flux. Superior cervical gangliectomy (SCGx)induces complete and irreversible ipsilateral choroid denervation. The aim ofthis work was to analyze the effect of SCGx on the retina/RPE in mice. Methods : Unilateral SCGx wasinduced in adult male C57BL/6J mice, while the contralateral side was submittedto a sham procedure, without excision of SCG (control). At 4, 6, and 10 weeksafter SCGx, retinal function (electroretinography, ERG), RPE melanin content(histology), all-trans retinyl ester binding protein (RPE65) levels(immunohistochemistry), retinal histology (toluidine blue), FR and RPEapoptosis (TUNEL assay), and choroid, Bruch′s membrane, RPE and FRultrastructure (electron microscopy) were assessed. Results : At 4 weeks post-SCGx,a significant decrease in scotopic ERG a-wave amplitude, which was even higherafter 6 and 10 weeks of SCGx was found, without changes in ERG b-wave oroscillatory potentials. SCGx induced a loss of the temporal (but not nasal) RPEmelanin content and RPE65 levels at 4 weeks post-SCGx, which was greater at 6and 10 weeks post-SCGx. At 10 weeks after SCGx, TUNEL(+) cells were found inthe temporal retinal outer nuclear layer and temporal RPE, while no TUNEL(+)cells were observed in the nasal side at all time points. After 4 weeks, SGCxinduced a significant increase in choriocapillaris thickness both in the nasaland temporal side, which persisted after 10 weeks of surgery, while no changesin total choroid thickness was found neither in the nasal nor in the temporalside in all experimental groups. After 6 and 10 weeks of SGCx, we found asignificant increase Bruch′s membrane thickness and RPE and FR outer segmentmorphological alterations in the temporal (but not nasal) side. Conclusions : These resultsshow that SCGx induced alterations which are compatible with GA in the retinaof the mice.