Abstract
Abstract: :
Purpose: Vitreous lactate concentrations are raised in ocular vascular diseases and in glaucoma eyes obtained during vitrectomy. Recently we found vitreous lactate to be higher in a rabbit model in which intraocular pressures (IOP) had been mechanically raised by intra–anterior chamber injections of latex beads. The present study was designed to determine whether this model could be validated as a model of experimental intraocular hypertension. Methods: Twenty–four albino rabbits were used. Group1 consisted of 20 rabbits that received a single 50µl injection of 20µm beads into the anterior chamber, while 4 other rabbits received a second injection four days after the first and were placed in group2. The contralateral eyes in all rabbits served as the control by receiving a sham injection of normal saline. IOP was measured with a Tono–pen while proton nuclear magnetic (1H–NMR) spectroscopy was used to non–invasively identify and measure vitreous lactate concentrations over time. Animals were euthanized at weekly intervals post–treatment, the eyes dissected and retinal wholemounts incubated in anti–PGP9.5, which labels for a neuron specific protein found in retinal ganglion cells (RGC). Labeled RGC were counted using light microscopy at 40x magnification. Results: Mean baseline IOP was 8±1 for the control eyes and 8.6±2mmHg for both treated groups. Mean IOP of the treated groups at weeks 1–3 (group1:16± 2, 14± 2, 12± 2mmHg; group2:17± 2, 25± 2, 13± 2mmHg) was significantly higher than controls (8±1, 9±2, 8±2;P≤0.05). Baseline lactate levels were 6.2± 2.5 and 5±2mM for the control and treated groups respectively. Although eyes that received 2 injections of latex beads had higher peak IOP (25±3mmHg) and vitreous lactate levels (20±4.1mM) compared with those that received 1 injection (14±2mmHg and10±1.9mM respectively), the difference in IOP and lactate concentration between the two groups was significant only at weeks 2 and 3 (P≤0.05). With a single treatment, RGC counts decreased throughout the study period from a baseline of 320,000±10,000 to 300,000±10,000 at week1, 280,000±15,000 at week2, 240,000±18,000 at week3, and 235,000±12,000 at week4. Conclusions: This model has demonstrated progressive RGC loss associated with elevation in IOP after a single 50µl injection of 20µm beads into the anterior chamber. There was also a concurrent and quantifiably significant increase in vitreous lactate. This together with our earlier findings suggests a role for lactate as a marker in experimental glaucoma.
Keywords: pathology: experimental • intraocular pressure • ganglion cells