Pathology of Natual Hypertension in the Florida Monkey Colony

Abstract

Abstract: : Purpose: Pathological changes in the optic nerve and retinal fiber layer may be strong evidence of primary open angle glaucoma (POAG). These data are valuable in understanding the Florida colony of naturally hypertensive (HT) rhesus monkeys (Macaca mulatta) and testing the hypothesis of associated pathology. Methods: Eyes were selected by independent expert panel. Unilateral enucleation choices were based on histories of quantitative indicators of POAG. Two had historical HT (> 18mmHg) (Dawson et al. BJO 1998) and high cup/disc (C/D) (0.5 – 0.7) by digital tomography (HRT). A third had high C/D and 14–16 mmHg pressure history. The age–matched controls had low pressures (< 13mmHg) and C/D histories (0.2–0.3). Parallel, independent evaluations (masked) were made of optic nerve axon density, cell pathology and fiber layer thickness (FLT) (macular–papillary and arcuate bundle regions). There were 3824, 98 x 98 micrometer, random (center or peripheral) fields counted for axons (Scion analysis). The data analysis was by 6 x 6 x 2 ANOVA. From each retina, 36 fiber layer thickness (digital) measures were made at each of the central and arcuate region sites (5 x 3 x 6 x 3 = 540). One retina was lost during processing. All procedures were approved by the IACUC. Results: Control fiber density was similar to published data for rhesus. Control vs. experimental F values for optic nerve regions and C/D were 32.6 and 49.2 where critical F = 7.08, p = 0.01. FLT mean reduction was 70 per cent in experimental retinas. ANOVA between the control and experimental FLT, p<0.001. Light and electron microscopy produced evidence for astrocyte infiltration and hypertrophy, gliosis, microvascular thickening and demyelination in the experimental nerves. Conclusions: Florida colony monkeys with historical C/D elevation show significant optic nerve axon and retinal fiber layer loss whether IOP’s are high or moderate. The cell pathology is consistent with optic nerve degeneration. However myelin sheath unwrapping of axons has not been reported before in early HT. This is the first report of quantitative histopathology in naturally ocular hypertensive monkeys.

Keywords: nerve fiber layer • intraocular pressure • pathology: experimental