June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Synaptic remodeling in a model of iatrogenic retinal detachment
Author Affiliations & Notes
  • Eva Halasz
    Pharmacology,Physiology, Neuroscience, Rutgers New Jersey Medical School, Newark, New Jersey, United States
  • Marco A Zarbin
    Department of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, Newark, New Jersey, United States
  • Ellen Townes-Anderson
    Pharmacology,Physiology, Neuroscience, Rutgers New Jersey Medical School, Newark, New Jersey, United States
  • Footnotes
    Commercial Relationships   Eva Halasz, Aerie Pharmaceuticals (F); Marco Zarbin, Aerie Pharmaceuticals (F); Ellen Townes-Anderson, Aerie Pharmaceuticals (F)
  • Footnotes
    Support  Department of Defense Grant 12753708, Research support from Aerie Pharmaceuticals
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3064. doi:
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      Eva Halasz, Marco A Zarbin, Ellen Townes-Anderson; Synaptic remodeling in a model of iatrogenic retinal detachment. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3064.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Retinal detachment (RD) creates synaptic damage in part by causing retraction of rod photoreceptor terminals from the outer plexiform layer. Reattachment surgery does not fully restore damaged synapses (Fisher et al. 2005). We have developed a model of iatrogenic detachment. This model mimics the detachment that occurs with subretinal injection of viral vectors or cells for repair of retinal disease. Here we explored the early events in synaptic remodeling that occur for an iatrogenic detachment followed by spontaneous reattachment.

Methods : RDs, about 4 optic disc diameters in size, were made in the nasal-inferior retinae of Yorkshire pigs by subretinal injection of balanced salt solution. Eyes were harvested 2 hrs or 2 days later and fixed for immunocytochemistry and confocal microscopy. Retina was examined both where detachment occurred and in areas where the retina remained attached. Synaptic retraction was quantified by image analysis of SV2-labeled synaptic vesicles in the outer nuclear layer (ONL). Rod bipolar cells (RBCs) were labeled for PKCα.

Results : At 2 hrs, retraction is present not only in detached retina but also in 2 attached areas, ~1-2 cm from the edge of the detachment, in the temporal- and nasal-superior quadrants. Although synaptic disjunction occurred in attached retina, the amount was less than in detached retina (p<0.01 n=4 pigs). By 2 days, the retina had reattached spontaneously. However, retraction remained in both the formerly detached and the attached retina. Comparing the level of retraction at 2 hrs and 2 days, there was a significant decrease in retraction in the formerly detached retina by 55% (p<0.05 n=9 pigs). This reduction was not due to reduced SV2 label; total label was unchanged in the outer retina from 2 hrs to 2 days (n=6 pigs). In addition, RBCs in both the formerly detached and attached regions had occasional long thin dendritic sprouts, extending into the ONL. These sprouts often contacted a retracted spherule.

Conclusions : Reattachment reduced retracted spherules in the formerly detached area, but retracted terminals remained. Whether synapses were reformed is not known. Moreover, by 2 days RBCs had sprouted in spite of retinal reattachment and damage in attached retina remained. Thus, early and extensive alterations in retinal circuitry may contribute to incomplete visual recovery after iatrogenic detachment.

This is a 2020 ARVO Annual Meeting abstract.

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