Electroretinographic abnormalities in a rat glaucoma model with chronic elevated intraocular pressure.

The purpose of this study was to determine the ability of electroretinographic (ERG) measurements to document progression of the retinopathy in a rat glaucoma model. Thirty four rats with a chronic intraocular pressure (IOP) elevation induced in one eye by cautery of three episcleral/extra-orbital veins were studied in four separate groups. ERGs were recorded sequentially in Group A rats (n = 12) at baseline, and after approximately 20, 40 and 60 days of high IOP, and in three additional groups of rats (n = 6 or 10 per group) after approximately 58, 30 and 175 days of high IOP, respectively. Scotopic ERG parameters recorded simultaneously from both eyes in Group A rats were: a- and b-wave amplitudes, implicit times, oscillatory potential amplitudes (OPs) determined at three different light-flash intensities, and the light-adapted (photopic) ERG b-wave amplitude. In the other groups of rats, only scotopic ERG a-wave, b-wave and OP amplitudes were measured.In Group A rats that were followed sequentially, all the ERG parameters recorded with attenuated stimuli showed significant time-dependent changes in glaucomatous eyes relative to their contralateral normal eyes, with OPs showing the earliest significant difference after only 3 weeks of high IOP. When different groups of unilateral glaucomatous rats were compared beyond 8 weeks of elevated IOP only the OPs showed a continued decrease with time and good discrimination between glaucoma and normal eyes. Over a 25 week period of high IOP the scotopic OPs measured with attenuated light stimuli declined at the rate of approximately 1.5% per week and provided the best ERG measure to monitor progression of retinal pathophysiology in the vein-occlusion rat glaucoma model.

The induction/impact tonometer: a new instrument to measure intraocular pressure in the rat.

Non-invasive intraocular pressure (IOP) measurement in rats can be performed with a variety of methods, none of which seems appropriate for scaling down for the mouse eye. In an attempt to develop such a method for non-invasive IOP measurement in mice, an alternative concept, that of rebound tonometry, was explored using an induction/impact (I/I) tonometer probe. IOP measurement using the rebound concept is based on bouncing a probe onto the eye and detecting its motion. Motion parameters of the probe, which vary according to eye pressure, are used to calculate the IOP. As a first step towards this goal a prototype I/I tonometer was evaluated for IOP measurement of the rat eye. Two similar instruments were constructed and tested for their ability to measure accurately and reliably rat IOP by comparing the measurements against the manometric (true) IOP as determined by cannulation ex vivo. Good correlation between the true IOP and the I/I measurements (R(2) = 0.95) was detected for IOP between 7.4 and 56 mmHg. Although individual eyes tested showed some variability in the relationship of the measured IOP with the true IOP, this variability was minimal. Starting probe-cornea distance between 3 and 5 mm, and angle of impact up to 25 degrees relative to the visual axis at the corneal apex, did not affect the reproducibility of the I/I tonometer. Comparison of I/I tonometer measurements to direct manometric determination of IOP by in vivo cannulation of eyes in anesthetized normal female Wistar rats correlated reasonably well (R(2) = 0.67) with manometrically determined IOP within the narrow range of normal rat IOPs (10-16.5 mmHg), underestimating the true (manometric) IOP by an average of 11.6%. The I/I tonometer is a reliable and accurate instrument for non-invasive IOP measurement in rat eyes that can potentially be adapted for IOP measurement in mice.

Diffuse retinal hemorrhages (ocular decompression syndrome) after trabeculectomy with mitomycin C for neovascular glaucoma.

PURPOSE: To describe a case of ocular decompression syndrome in a patient after trabeculectomy with mitomycin C for neovascular glaucoma. RESULTS: Diffuse retinal hemorrhages developed in the posterior pole of a patient with neovascular glaucoma after he underwent trabeculectomy with mitomycin C. The hemorrhages persisted for less than 9 months. CONCLUSIONS: Acute decompression of the eye in patients with high intraocular pressure can lead to the development of posterior pole hemorrhages. The course of this rare syndrome is relatively benign.

Retinal damage after 3 to 4 months of elevated intraocular pressure in a rat glaucoma model.

PURPOSE: To characterize a long-term elevated intraocular pressure (IOP) glaucoma model in the rat with respect to electroretinographic (ERG) changes and the pattern and mechanism of retinal ganglion cell (RGC) death. METHODS; An approximate doubling of IOP was induced in one eye (G) of female Wistar rats (150-180 g) by cautery of 3 episcleral/limbal veins. At intervals over 3 to 4 months, measurements of IOP and ERG changes (contact-lens electrode) were made in both the G and contralateral normal (N) eyes. At the end of 3 to 4 months of elevated IOP, RGCs were fluorescently labeled with Fluorogold (retrogradely from the superior colliculus), or retinas were labeled by intravitreal injection of a mitochondrial potential indicator dye and stained for apoptotic nuclei with a DNA dye. Flatmounts of fixed, dye-labeled retinas were examined by epifluorescence, confocal, or interference contrast microscopy. RESULTS: Elevated IOP was consistently maintained for up to 4 months in G eyes, but ERG a- and b-waves showed a statistically significant decline, of 30% to 40% in amplitude, after 3 months. Loss of RGCs in G retinas was primarily focal with no statistically significant loss demonstrable outside of the focal areas when assessed by an area sampling method for counting RGCs, which totaled 2% to 3% of the entire retinal area. Mitochondrial membrane potential of cells in the RGC layer was reduced by 17.5% (P: < 0.05) in regions surrounding areas of focal loss compared with comparable locations in control N eyes. After 3.5 months' elevated IOP the G retinas showed cell nuclei at various stages of apoptosis, from initial DNA condensation to fragmentation. CONCLUSIONS: The three-vein episcleral/limbal vein occlusion model for inducing glaucomatous pathology in the rat eye gives a consistent long-term elevation of IOP. After 3 to 4 months of approximately 100% increased IOP, the ERG responses begin to decline, there is a variable focal loss of RGCs, and some of the remaining RGCs show characteristics of stress and apoptosis. These changes seem consistent with retinal damage in human glaucoma (focal field defects), and this rat model appears to mimic some features of primary open-angle glaucoma.

CNS myelin and sertoli cell tight junction strands are absent in Osp/claudin-11 null mice.

Oligodendrocyte-specific protein (OSP)/claudin-11 is a recently identified transmembrane protein found in CNS myelin and testis with unknown function. Herein we demonstrate that Osp null mice exhibit both neurological and reproductive deficits: CNS nerve conduction is slowed, hindlimb weakness is conspicuous, and males are sterile. Freeze fracture reveals that tight junction intramembranous strands are absent in CNS myelin and between Sertoli cells of mutant mice. Our results demonstrate that OSP is the mediator of parallel-array tight junction strands and distinguishes this protein from other intrinsic membrane proteins in tight junctions. These novel results provide direct evidence of the pivotal role of the claudin family in generating the paracellular physical barrier of tight junctions necessary for spermatogenesis and normal CNS function.

Iridoschisis: high frequency ultrasound imaging. Evidence for a genetic defect?

AIMS: To elucidate changes in the anatomy of the anterior chamber associated with iridoschisis, a rare form of iris atrophy, and their potential contribution to angle closure glaucoma. METHODS: Both eyes of a 71-year-old woman with bilateral iridoschisis and fibrous dysplasia and her asymptomatic 50-year-old daughter were scanned with a very high frequency (50 MHz) ultrasound system. RESULTS: The symptomatic patient exhibited diffuse changes in the iris stoma with an intact posterior iris pigmented layer in both eyes. These changes were clinically compatible with the lack of iris transillumination defects. Additionally, iris bowing with a resultant narrowing of the angle occurred. The asymptomatic daughter showed discrete, but less severe iris stromal changes. CONCLUSION: This is the first detailed study of high frequency ultrasonic imaging of the iris in iridoschisis. The observed structural changes suggest angle narrowing by forward bowing of the anterior iris stroma may be a mechanism of IOP elevation in this condition. The ultrasonic detection of iris changes in the asymptomatic daughter of the symptomatic patient and the association of iridoschisis with fibrous dysplasia suggest a possible genetic component in the pathogenesis of this condition.

Expression of IGF-I and IGF-II genes in the adult rat eye.

We have investigated the transcription of IGF-I and IGF-II genes in the adult rat eye. Each eye was dissected into cornea, lens, sclera + choroid + pigment epithelium, and neural retina. Total cellular RNA was isolated from each of these tissues. Northern blot analysis using rat coding region cDNA probes revealed the presence of IGF-I and IGF-II specific transcripts in the retina and the sclera but not in the lens and cornea. Retina demonstrated the highest level of IGF-I and IGF-II expression. Our results suggest autocrine and paracrine effects of the IGFs and their possible involvement in normal eye physiology as well as in the pathogenesis of certain eye diseases.