ABSTRACT
PURPOSE: To develop an inducible mouse model of glaucoma. METHODS: An obstruction of aqueous humor outflow in adult C57BL6/J mice was induced by combined injection of indocyanine green (ICG) dye into the anterior chamber and diode laser treatment. To evaluate intraocular pressure (IOP), tonometry was performed with a modified Goldmann tonometer. The function of the retina was evaluated with electroretinography (ERG). RESULTS: IOP was significantly elevated in surgical eyes compared with control eyes: before surgery, 15.2 +/- 0.6 mm Hg; 10 days after surgery, 33.6 +/- 1.5 mm Hg (P < 0.001); and 30 days after surgery, 27.4 +/- 1.2 mm Hg (P < 0.001). However, 60 days after surgery, IOP in the surgical eyes decreased to 19.5 +/- 0.9 mm Hg and was not significantly different compared with control eyes (control, 17.3 +/- 0.7 mm Hg; P = 0.053). ERG amplitudes, expressed as a ratio (surgical/control), were decreased in surgical eyes. The amplitudes for b-wave were: before surgery, 107.6% +/- 4.6%; 28 days after surgery, 61% +/- 4% (P < 0.001); and 56 days after surgery, 62% +/- 5.6% (P < 0.001). Oscillatory potentials were the most dramatically affected: before surgery, 108.6% +/- 6.7%; 28 days after surgery, 57.5% +/- 5% (P < 0.01); and 56 days after surgery, 57% +/- 8.5% (P < 0.001). Amplitudes of the a-waves had relatively smaller but still significant deficits: before surgery, 105.8% +/- 6.9%; 28 days after surgery, 72.2% +/- 5.4% (P < 0.01); and 56 days after surgery, 79.8% +/- 11.0% (P < 0.01). Histologic analysis of the surgical eyes revealed development of anterior synechia, loss of retinal ganglion cells (RGCs), and thinning of all retinal layers. Electron microscopy of optic nerve cross sections revealed swelling and degeneration of the large diameter axons and gliosis. CONCLUSIONS: Diode laser treatment of ICG saturated episcleral veins causes a chronic elevation of IOP and sustained ERG deficits.
Subject(s)
Disease Models, Animal , Laser Therapy , Ocular Hypertension/pathology , Trabecular Meshwork/surgery , Animals , Aqueous Humor/metabolism , Chronic Disease , Electroretinography , Fluorophotometry , Indocyanine Green , Intraocular Pressure , Mice , Mice, Inbred C57BL , Ocular Hypertension/metabolism , Optic Nerve/pathology , Oscillometry , Retinal Ganglion Cells/pathology , Tonometry, Ocular , Trabecular Meshwork/metabolism , Trabecular Meshwork/pathologyABSTRACT
PURPOSE: To characterize the pupil light reflex (PLR), electroretinographic (ERG) and tonometric parameters which might be of importance for the in vivo characterization of mouse models of chronic ocular hypertension. METHODS: C57/BL6 mice were used for experiments. The PLR was evaluated with a computerized pupillometer (n = 14), ERGs were recorded simultaneously from both eyes (n = 23) and IOP was measured with a modified Goldmann tonometer (n = 23). RESULTS: The analysis of the PLR parameters confirmed the consensual PLR did not have significantly different amplitude (p > 0.1) and latency time (p > 0.1) compared to the direct PLR. However, PLR velocity (p = 0.004) was significantly smaller in the consensual PLR. Electroretinography revealed a-wave amplitude of 168.3 +/- 9.6 microV with latency of 27.5 +/- 0.6 ms and b-wave 403 +/- 28.8 microV with latency of 22.7 +/- 0.6 ms. The flicker ERG recording revealed amplitudes of 20.6 +/- 2.4 microV. Tonometry experiments revealed that modified Goldmann tonometer measurements correlated well with invasive manometry (r(2) = 0.89). The mean IOP of the mouse was 15.3 +/- 0.6 mmHg. CONCLUSIONS: Consensual PLR in mice is relatively slower than the direct PLR, but retains the same degree of constriction comparing to the direct PLR. A modified Goldmann tonometer seems to be a reliable non-invasive tool for IOP measurements in mice.
