A Novel Pig Model of Glaucoma: Retinal Ganglion Cell Death After Chronic Elevation of Intraocular Pressure

Abstract

Abstract: : Purpose: To validate the pig eye as a model of glaucoma, based on chronic elevation of intraocular pressure (IOP). Methods: IOP was elevated by cauterizing 3 episcleral veins in the left eyes of three adult pigs. Right eyes were used as controls. Measurement of IOP was performed with an applanation tonometer (Tono–Pen). Six months after episcleral vein occlusion, retinal ganglion cells (RGC) from both cauterized and control eyes were retrogradely backfilled with Fluoro–Gold. Analysis of RGC loss and morphometric characterization of surviving RGCs was performed using whole–mounted retinas. The morphology of the RGCs was analyzed by the use of the lipophylic tracer DiI in fixed control adult pig eyes. Results: Elevation of IOP after cauterization of the epiescleral veins was apparent by the 3rd week and remained elevated throughout the duration of the experimental period. Elevation of IOP led to significant RGC death in the peripheral and mid–peripheral retina. Thus RGC density (RGC/ mm²) in the peripheral retina was 239 ± 28 in controls vs 188 ± 23 in cauterized eyes. In the mid–periphery the mean RGC density was 838 ± 34 in controls and 727 ± 27 in cauterized eyes. A more detailed analysis revealed that RGC loss was greater in the temporal quadrants. Moreover the mean soma area (µm²) of the remaining RGCs was increased. Thus, in the periphery the mean RGC soma area was 298 ± 8 in controls vs. 328 ± 16 in cauterized eyes, and in the mid–periphery 235 ± 3 in controls vs. 244 ± 4 in cauterized eyes. RGC size and dendrite maps are reported as a function of retina eccentricity. Conclusions: The pattern of RGC death induced in the pig retina by episcleral vein cauterization resembles that found in human glaucoma. The pig retina may be considered as a suitable model for glaucoma–related studies, based on its similarity with the human retina and on its affordability.

Keywords: retina • intraocular pressure • ganglion cells