Abstract
Purpose :
Age related macular degeneration (AMD) is a main cause of irreversible blindness. AMD is classified in two forms: wet or neovascular, and dry or geographic atrophy (GA). GA is characterized by hypopigmentation of the retinal pigment epithelium (RPE) and photoreceptor (FR) loss in a localized area of the retina. Alterations in choroid blood flow have been related in the pathogenesis of GA. Sympathetic terminals from the superior cervical sympathetic ganglion (SCG) innervate choroid vessels and modulate their flux. Superior cervical gangliectomy (SCGx) induces complete and irreversible ipsilateral choroid denervation. The aim of this work was to analyze the effect of SCGx on the retina/RPE in mice.
Methods :
Unilateral SCGx was induced in adult male C57BL/6J mice, while the contralateral side was submitted to a sham procedure, without excision of SCG (control). At 4, 6, and 10 weeks after SCGx, retinal function (electroretinography, ERG), RPE melanin content (histology), all-trans retinyl ester binding protein (RPE65) levels (immunohistochemistry), retinal histology (toluidine blue), FR and RPE apoptosis (TUNEL assay), and choroid, Bruch′s membrane, RPE and FR ultrastructure (electron microscopy) were assessed.
Results :
At 4 weeks post-SCGx, a significant decrease in scotopic ERG a-wave amplitude, which was even higher after 6 and 10 weeks of SCGx was found, without changes in ERG b-wave or oscillatory potentials. SCGx induced a loss of the temporal (but not nasal) RPE melanin content and RPE65 levels at 4 weeks post-SCGx, which was greater at 6 and 10 weeks post-SCGx. At 10 weeks after SCGx, TUNEL(+) cells were found in the 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, SGCx induced a significant increase in choriocapillaris thickness both in the nasal and temporal side, which persisted after 10 weeks of surgery, while no changes in total choroid thickness was found neither in the nasal nor in the temporal side in all experimental groups. After 6 and 10 weeks of SGCx, we found a significant increase Bruch′s membrane thickness and RPE and FR outer segment morphological alterations in the temporal (but not nasal) side.
Conclusions :
These results show that SCGx induced alterations which are compatible with GA in the retina of the mice.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.