Loss of retinal tension and permanent decrease in retinal function: a new porcine model of rhegmatogenous retinal detachment

Abstract

Purpose: Permanent loss of visual function after rhegmatogenous retinal detachment can occur despite successful surgical reattachment in humans. New treatment modalities could be explored in a detachment model with loss of retinal function. In previous porcine models, retinal function has returned after reattachment, regardless of height and duration of detachment. Difference in retinal tension between the models and the disease might explain these different outcomes. This study investigates, for the first time in an in vivo porcine model, another characteristic of rhegmatogenous retinal detachment - the loss of retinal tension.

Methods: Left eyes (n = 12) of 3-month-old domestic pigs were included. Baseline multifocal electroretinogram (mfERG) and a fundus photograph were obtained following anaesthesia (isoflurane). The pigs were vitrectomized, saline was injected subretinally, and the RPE was removed. The eyes were evaluated at 2, 4 and 6 weeks after surgery. Four eyes were enucleated at each evaluation for histologic examinations.

Results: A retinal detachment structurally resembling rhegmatogenous retinal detachment was induced in 11 out of 12 pigs. MfERG amplitudes were significantly decreased despite partial reattachment four and 6 weeks after detachment. The retinal thickness decreased with 27%, the inner nuclear layer degenerated, Müller cells hypertrophied, and outer segments were lost. In the ganglion cell layer, cellularity increased and there was cytoplasmic staining with Cyclin D1. Vimentin and GFAP staining for glial cells increased. After 2 weeks of detachment, the ganglion cells had lost their nucleus and nucleolus.

Conclusions: Loss of retinal tension in the detached retina seems to induce permanent damage with loss of retinal function. Death of ganglion cells, observed as soon as 2 weeks after detachment, explains the permanent loss of retinal function. The new model enables investigations of time-relationship between retinal detachment and lasting damage in addition to exploration of novel treatment modalities.

Keywords: Neuroprotection; RPE damage; animal model; intermediate filaments; mammal; retinal surgery; subretinal surgery.