Irregular retinal and RPE damage after pressure-induced ischemia in the rabbit

PURPOSE: Pressure-induced ocular ischemia is a frequent model for the investigation of the mechanisms and therapy of retinal ischemic damage. It is important to know whether the tissue damage in such experiments is uniform or irregular. METHODS: We reviewed histologic features of Dutch rabbit eyes after 60-80 min of pressure-induced ischemia. The eyes were enucleated 4 hr, 1 day, or 1 wk after circulation was restored, at which times the electroretinogram b-wave was moderately reduced. RESULTS: Light microscopy showed an irregular distribution of damage involving all retinal layers and retinal pigment epithelium. Some regions of damage (or preservation) were several millimeters wide; others were as small as a few cell widths. Correlation with electroretinogram reduction in individual eyes was difficult. CONCLUSIONS: These results show that pressure-induced ischemic damage in the rabbit, sufficient to reduce the electroretinogram, has a patchy and irregular effect on retina and retinal pigment epithelium. Erroneous judgments may be made about ischemic damage, or therapeutic intervention, if only small or selected regions of retina are examined histologically.     

Tumors of the eye and ocular adnexal tissues

This article reviews options in dealing with tumors of the cornea and conjunctiva, nictitating membrane neoplasms, and eyelid neoplasms. Orbital tumors, optic nerve and other intraocular tumors are also discussed.     

Chronic ocular ischemia associated with the Eisenmenger's syndrome

We studied the ocular findings of two adult patients with the Eisenmenger's syndrome who had atrial septal defects that were diagnosed before the age of 10 years but not operated on and pulmonary hypertension. Both eyes of these patients showed microaneurysms, multiple small blot hemorrhages, or capillary dilation in the temporal peripheral fundus. Multiple microaneurysms and retinal collaterals were confirmed by fluorescein angiography. One of the patients developed bilateral rubeosis iridis with slow progression. These retinal lesions and the rubeosis iridis are probably related to chronic ocular ischemia caused by chronic systemic hypoxia.     

Membrane type-1 matrix metalloproteinase in human ocular tissues

PURPOSE: Membrane type-1 matrix metalloproteinase (MT1-MMP) (MMP-14) (EC 3.4.24.xx) is involved in the activation of progelatinase A (MMP-2) (EC 3.4.24.24). MMP-2 is present at least in the interphotoreceptor matrix and vitreous. The purpose of this study was to determine the distribution of MT1-MMP, and MMP-2, in human ocular tissues. METHODS: The distribution of MT1-MMP and MMP-2 was investigated in vitreous and in membrane extracts from eye tissues obtained from postmortem human eyebank eyes. Western blot analysis was performed using mouse monoclonal anti-MT1-MMP and anti-MMP-2 antibodies. RESULTS: MT1-MMP was found in sclera, cornea, lens, choroid, retinal pigment epithelium (RPE) and retina. MMP-2 was found in sclera, cornea, choroid, vitreous, RPE and retina but was absent from lens. CONCLUSION: We provide the first evidence for the presence and distribution of membrane-type-1 matrix metalloproteinase in human ocular tissues. MT1-MMP may be responsible for the activation of progelatinase A in many ocular extracellular matrices in a manner similar to that exhibited in other systems.     

Endothelin expression in ocular tissues of diabetic and insulin-treated rats

PURPOSE: The endothelins are potent vasoactive peptides that are widely distributed in ocular tissues. There is evidence linking the endothelins to vascular dysfunction in diabetic microangiopathy. Thus, the synthesis and distribution of endothelin-1 (ET-1) and endothelin-3 (ET-3) were studied in the retinas of diabetic and nondiabetic animals. METHODS: Levels of ET-1 and ET-3 were determined by radioimmunoassay in ocular tissues of normal rats, and in rats with streptozotocin-induced diabetes of 6 and 12 weeks' duration, insulin-treated and untreated. In a separate cohort of similarly treated animals, retinal vascular trypsin digest preparations were immunostained, using antibodies raised against ET-1 and ET-3. RESULTS: Ocular ET-1 levels were elevated twofold in diabetic animals that received insulin treatment for 7 days when compared with levels in normal rats. Insulin treatment for 10 days before death caused a fourfold elevation of ET-1 in ocular tissues. Endothelin-1 was also increased in 12-week-old diabetic animals and in those maintained on insulin throughout their period of diabetes. Immunofluorescence to anti-ET-1 within the capillary bed and veins of the retina in diabetic insulin-treated animals was elevated when compared with digests from normal litter-matched control animals. Ocular tissue ET-3 levels were unaffected by diabetes. CONCLUSIONS: Overall ocular and retinal tissue levels of ET-1 were selectively elevated by diabetes and insulin treatment, suggesting that the endothelins may be involved in the pathogenesis of diabetic retinal microangiopathy.     

Diffusion-weighted MR imaging of acute cerebral ischemia

Diffusion-weighted MR imaging has been used in studies on experimental animal models and on patients with acute cerebral ischemia. Compared with CT and conventional MR techniques, diffusion-weighted imaging can provide earlier and more precise detection of the location and the extent of an ischemic lesion during the critical first few hours after the onset of stroke. Quantitative apparent diffusion coefficient (ADC) mapping of the brain water can also be carried out by recording a series of diffusion-weighted images with different amplitudes of the displacement encoding gradients. ADC maps can provide important information about the extra- and intracellular water homeostasis. ADC reduction of the tissue water is one of the early signals of the pathophysiological cascade resulting from ischemic tissue injury. Diffusion MR imaging has become a valuable tool in stroke research. It may also prove a valuable tool in monitoring the efficiency of therapeutic effects in stroke patients. It is our intention to provide an overview of the recent development in this area with emphasis on the diffusion-weighted MR techniques, and to discuss the possible underlying biophysical mechanisms responsible for the contrast of diffusion-weighted imaging.     

Cortical Responses in Rats Predict Perceptual Sensitivities to Complex Sounds.

The common assumption that perceptual sensitivities are related to neural representations of sensory stimuli has seldom been directly demonstrated. The authors analyzed the similarity of spike trains evoked by complex sounds in the rat auditory cortex and related cortical responses to performance in an auditory task. Rats initially learned to identify 2 highly different periodic, frequency-modulated sounds and then were tested with increasingly similar sounds. Rats correctly classified most novel sounds; their accuracy was negatively correlated with acoustic similarity. Rats discriminated novel sounds with slower modulation more accurately than sounds with faster modulation. This asymmetry was consistent with similarities in cortical representations of the sounds, demonstrating that perceptual sensitivities to complex sounds can be predicted from the cortical responses they evoke. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Induced acute ocular hypertension: mode of retinal cell degeneration

The effects of experimental hypertension on retinal cells were studied. Evaluation was made of IOP levels and degree of cell damage by cytochemical and DNA analysis, and degeneration modes: necrosis and apoptosis.     

Expression and localization of angiotensin II type 1 receptor mRNA in rat ocular tissues

OBJECTIVE: Hereditary hemorrhagic telangiectasia (HHT) is an inherited abnormality passed down as a dominant autosomal feature. Recurrent epistaxis usually constitutes the major clinical manifestation of this disease. The unsatisfactory results of conservative therapy have stimulated a research interest for the role of laser photocoagulation in telangiectatic vessels associated with this clinical entity. METHOD: The Nd:YAG laser was used to treat a group of 11 individuals suffering from HHT, all of whom had been previously treated using other modalities. RESULTS AND CONCLUSION: The excellent results of Nd:YAG laser irradiation are addressed in view of all treatment modalities proposed for the treatment of recurrent epistaxis in HHT.     

Choline acetyltransferase in ocular tissues of rabbits, cats, cattle, and man

The variation of choline acetyltransferase activity in ocular tissues of four mammalian species, rabbits, cats, cattle, and man, was determined. Enzyme activity of irides and ciliary bodies, i.e., parasympathetically innervated structures, tended to be similar in all four species. Two exceptions were bovine irides and human ciliary bodies; these two tissues had higher enzyme activities. Choline acetyltransferase activity was present in the corneal epithelium of rabbit, bovine, and human eyes, but little or none could be detected in that of cats. Feline retina and pigment epithelium-choroid also contained far less choline acetyltransferase activity than the same tissues in the other three species.     

Expression of herpes simplex associated antigens in ocular tissues following induced herpetic anterior uveitis

Timing and distribution of the expression of herpes simplex virus, type 1, associated antigen (HSV-1 AA) positive cells were studied immunohistochemically, following unilateral inoculation of HSV-1 into the anterior chamber of BALB/c mice. Inflammatory cells appeared in the corneal limbus, the anterior chamber angle, and Schlemm's canal of the inoculated eyes within 24 hours. HSV-AA positive cells developed in this period in the non-pigmented epithelium (which corresponds to the human pigmented epithelium) of the iris and the corneal endothelium; they also appeared in the ciliary body by the day 3 and remained positive until day 7. Apparent involvement of the posterior segment of the eye was seen in only 2 of the 9 inoculated eyes on day 3. However, once invasion of the posterior segment has occurred, there appears to be a stronger reaction in the retinal non-pigmented epithelial (RnPE) layer, which corresponds to the human retinal pigmented epithelium, than in the sensory retina.     

Three-dimensional distribution of ST-T wave alternans during acute ischemia

INTRODUCTION: A canine model of reversible ischemia was used to measure the magnitude and transmural distribution of repolarization alternans. METHODS AND RESULTS: Twenty-four multielectrode needles were inserted into a reversibly ischemic region created by 8 minutes of coronary occlusion. One hundred ninety-two unipolar electrograms were simultaneously recorded at 1-minute intervals for 8 minutes of ischemia and 3 minutes of reflow recovery. Beat-to-beat repolarization alternans was quantified for all electrograms using the standard deviation of QRST integrals. When alternans from animals that fibrillated was compared with alternans from animals that did not, the magnitude of alternans in the fibrillation group was an average standard deviation of 1125 +/- 99.7 mV-msec at the time of fibrillation and 409 +/- 183 mV-msec at 8 minutes of ischemia in the animals that did not fibrillate. The increase in alternans occurred mainly in the mid-myocardial and epicardial regions in the animals that fibrillated. QRS morphology of sequential electrograms did not differ in beat-to-beat comparison, suggesting that repolarization alternans measured was not due to alternating conduction block in the region of reversible ischemia. CONCLUSION: During acute ischemia, the magnitude and distribution of repolarization alternans are greater and differ in hearts that experience ventricular fibrillation. This observation may have clinical utility in arrhythmia prediction. It also is consistent with the possibility there may be multiple mechanisms for repolarization alternans.     

Variability of choline acetyltransferase in ocular tissues of rabbits, cats, cattle and humans

It has been proved in three rodent species that in the insoluble collagen fraction which accumulates in skin collagen with age of the two categories of collagen present (collagen type I and collagen type III), their proportion alters in favour of collagen type I with the advancing age. Since it has also been shown that collagen type I is less resistant towards proteolytic cleavage than is collagen type III its accumulation can be explained either by rapidly advancing cross-linking of this collagen type or more likely by different proteosynthesis. The second alternative is preferred since a step-wise polymerization of collagen type III was also observed. No information revealing to what extent the lysine derived cross-links can combine both collagen types is at present available. On the basis of this information the rapid decrease in insoluble collagen in very early ontogeny (rats below 8 weeks of age) is explained.