Laser-induced mouse model of chronic ocular hypertension

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 Ϯ 0.6 mm Hg; 10 days after surgery, 33.6 Ϯ 1.5 mm Hg (P Ͻ 0.001); and 30 days after surgery, 27.4 Ϯ 1.2 mm Hg (P Ͻ 0.001). However, 60 days after surgery, IOP in the surgical eyes decreased to 19.5 Ϯ 0.9 mm Hg and was not significantly different compared with control eyes (control, 17.3 Ϯ 0.7 mm Hg; P ϭ 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% Ϯ 4.6%; 28 days after surgery, 61% Ϯ 4% (P Ͻ 0.001); and 56 days after surgery, 62% Ϯ 5.6% (P Ͻ 0.001). Oscillatory potentials were the most dramatically affected: before surgery, 108.6% Ϯ 6.7%; 28 days after surgery, 57.5% Ϯ 5% (P Ͻ 0.01); and 56 days after surgery, 57% Ϯ 8.5% (P Ͻ 0.001). Amplitudes of the a-waves had relatively smaller but still significant deficits: before surgery, 105.8% Ϯ 6.9%; 28 days after surgery, 72.2% Ϯ 5.4% (P Ͻ 0.01); and 56 days after surgery, 79.8% Ϯ 11.0% (P Ͻ 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. (Invest Ophthalmol Vis Sci. 2003;44:4337-4346

Topical ocular sodium 4-phenylbutyrate rescues glaucoma in a myocilin mouse model of primary open-angle glaucoma

PURPOSE. Mutations in the myocilin gene (MYOC) are the most common known genetic cause of primary open-angle glaucoma (POAG). The purpose of this study was to determine whether topical ocular sodium 4-phenylbutyrate (PBA) treatment rescues glaucoma phenotypes in a mouse model of myocilin-associated glaucoma (Tg-MYOC Y437H mice). METHODS. Tg-MYOC Y437H mice were treated with PBA eye drops (n ϭ 10) or sterile PBS (n ϭ 8) twice daily for 5 months. Long-term safety and effectiveness of topical PBA (0.2%) on glaucoma phenotypes were examined by measuring intraocular pressure (IOP) and pattern ERG (PERG), performing slit lamp evaluation of the anterior chamber, analyzing histologic sections of the anterior segment, and comparing myocilin levels in the aqueous humor and trabecular meshwork of Tg-MYOC Y437H mice. Sci. 2012;53: 1557-1565 RESULTS. Tg-MYO

2003b. Functional characterization of retina and optic nerve after acute ocular ischemia in rats

PURPOSE. To functionally characterize the status of the rat retina and optic nerve after acute elevation of intraocular pressure (IOP) and to determine the dynamics of the pathologic changes in the ischemic retina and optic nerve. METHODS. Retinal ischemia was induced in rats by acutely increasing the IOP (110 mm Hg/60 minutes). Direct and indirect pupil light reflexes (PLRs) were recorded from the noninjured eye, and electroretinograms (flash and flicker ERG) were recorded from the injured and control eyes before and after surgery. Amplitudes and latencies were calculated for each recording session. RESULTS. Preoperative PLR ratio s (indirect/direct PLR) were 76.7 Ϯ 2.6 (mean Ϯ SEM). Twenty-four hours after surgery the PLR ratio was 15.2 Ϯ 12.8, 10 days after surgery, 11.6 Ϯ 9.8; 20 days after surgery, 26.5 Ϯ 8.0; and 28 days after surgery, 33.27 Ϯ 9.3. However, at day 35, the PLR had significantly recovered (41.1 Ϯ 7.3) when compared with the 24-hour postoperative ratios (P Ͻ 0.01, repeated-measures ANOVA). Forty-two days after surgery, the PLR ratio started to decrease once again in the injured eyes (28.7 Ϯ 5.9). Electroretinographic amplitudes (full-field flash ERG) followed a similar pattern. Cone responses (flicker ERG) were measured 42 days after surgery and revealed defects in injured eyes (control eyes: 46.6 Ϯ 2.9 V, injured eyes: 3.4 Ϯ 1.7 V). Histologic analysis revealed ischemic damage to all retinal layers, with the primary defects localized to the central retina. CONCLUSIONS. Acute ocular ischemia causes a significant decrease in retinal function, as measured by PLR and ERG, although over time the rat retina and optic nerve show partial regain of function. (Invest Ophthalmol Vis Sci. 2003;44: 2597-2605) DOI:10.1167/iovs.02-0600 I schemic insults to the retina and optic nerve are frequently observed in glaucoma, acute ocular hypertension, diabetic retinopathy, hypertension, and vascular occlusion, and giant cell arteritis and can lead to serious perturbation of neuronal and glial retinal elements and can ultimately lead to blindness. Traditionally, retinal damage due to ischemia has been considered a potentially incurable condition in humans and animals because of the mammalian central nervous system has no regenerative capacity. Few reports have described the recovery of visual function in patients who have severe retinal ischemia after central retinal artery occlusion, 1,2 whereas more reports have confirmed that severe ischemic events are followed by almost complete and irreversible loss of visual function. 10,11 However, quantitative analysis of the damage has been achieved only by end-stage counting of the cells in the different retinal layers 12 or retrograde fluorescent labeling of retinal ganglion cells (RGCs). 13 Relatively few studies have included a functional analysis of the retina after ischemia-reperfusion injury using electroretinography (ERG) for a prolonged period, 14 -16 and, to our knowledge, there is only one published study that actually documents function of the retina and optic nerve in rats after ischemia-reperfusion injury (Clarke RJ, Gamlin PDR, ARVO Abstract 4593, 1998). Although morphologic studies provide important information about the number of surviving cells, only electrophysiological studies offer precise information about the functional status of the retina and the dynamics of ischemic injury. MATERIALS AND METHODS Induction of Retinal Ischemia by Elevated IOP All animal studies were conducted in accordance with the ARVO Statement for Use of Animals in Ophthalmic and Vision Research, and procedures were approved by the Iowa State University Committee on Animal Care. A previously published procedure to generate an ischemia-reperfusion insult in rats was used, with slight modification

Functional and Structural Changes in a Canine Model of Hereditary Primary Angle-Closure Glaucoma

The principal purpose of this study was to describe a model of canine hereditary angle-closure glaucoma characterized by progressive increase in intraocular pressure, loss of optic nerve function, and retinal ganglion cell loss

Exploring Raman spectroscopy for the evaluation of glaucomatous retinal changes

Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cells and subsequent loss of visual function. Early detection of glaucoma is critical for the prevention of permanent structural damage and irreversible vision loss. Raman spectroscopy is a technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, we explored the potential of using Raman spectroscopy for detection of glaucomatous changes in vitro. Raman spectroscopic imaging was conducted on retinal tissues of dogs with hereditary glaucoma and healthy control dogs. The Raman spectra were subjected to multivariate discriminant analysis with a support vector machine algorithm, and a classification model was developed to differentiate disease tissues versus healthy tissues. Spectroscopic analysis of 105 retinal ganglion cells (RGCs) from glaucomatous dogs and 267 RGCs from healthy dogs revealed spectroscopic markers that differentiated glaucomatous specimens from healthy controls. Furthermore, the multivariate discriminant model differentiated healthy samples and glaucomatous samples with good accuracy [healthy 89.5% and glaucomatous 97.6% for the same breed (Basset Hounds); and healthy 85.0% and glaucomatous 85.5% for different breeds (Beagles versus Basset Hounds)]. Raman spectroscopic screening can be used for in vitro detection of glaucomatous changes in retinal tissue with a high specificity.This article is from Journal of Biomedical Optics 16 (2011): 107006, doi:10.1117/1.3642010.</p

Whole genome homozygosity mapping results.

<p>A red peak reaching a 1.0 max score of statistical significance depicts a homozygous region on chromosome 19. The region coincides with the 0.49 Mbp locus identified using two-point linkage analysis and is bracketed by recombination spots (indicated in red). The identified haploblock fulfills the zygosity criterion by displaying homozygosity in affected animals (indicated in red) and heterozygosity in unaffected carriers (indicated in green).</p