Abstract
Purpose :
Retinal edema is associated with visually impairing retinal diseases including diabetic retinopathy and macular degeneration, inflammation, retinal vein occlusion and surgical interventions. In each condition, vision loss is comorbid with retinal edema but the role of edema in visual impairment remains unknown. We established a new experimental model to study how retinal edema impacts visual function, and to explore the role of microglial cells in this process.
Methods :
Laser photocoagulation was used (argon laser, spot size 50 µm, power 160 mW, pulse duration 50 ms, 7-10 spots per vein) to induce retinal vein occlusion (RVO) in rose bengal-injected transgenic mice with GFP-expressing microglia (CX3CR1-GFP; n = 27). Retinal thickness was measured in vivo, using optical coherence tomography (OCT) at 8 time points following RVO (8h -14d). Microglia morphology and spatial distribution was evaluated using confocal microscopy.
Results :
RVO induced robust, reproducible edema as noted by OCT scans. Retinal thickness increased from 273 ± 3.1 pre RVO to 363 ± 48.7 µm at 8h and 296 ± 34.6 µm 1d post RVO (n = 5, 4, and 3); retinal thickness continued to decrease up to day 14 (232 ± 27.2 µm; n = 4), consistent with ischemia. RVO evoked a stereotyped microglia response. At days 1 and 2, microglia arboreal processes were visibly retracted and the density of resident microglia around the optic nerve head reduced, suggesting cell migration. After day 4, increased cell density of microglia and possibly infiltrated macrophages was apparent at the lesion sites.
Conclusions :
RVO causes retinal edema and a microglial response, each with a specific reproducible time course. The time window for evaluating retinal edema and its role in neuronal cell death and vision loss is 8-48 hours. The model permits assays for investigating the role of microglia in edema-associated visual impairment and may help guide the development of future treatments for the prevention of edema-associated irreversible vision loss in retinal diseases.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.