| 1. |
- Almegard, B, et al.
(författare)
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Outflow facility in the monkey eye: effects of calcitonin gene-related peptide, cholecystokinin, galanin, substance P and capsaicin
- 1990
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Ingår i: Experimental Eye Research. - 0014-4835. ; 51:6, s. 685-689
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Tidskriftsartikel (refereegranskat)abstract
- A study in cats has shown that intracameral injection of calcitonin gene-related peptide (CGRP) increases the outflow facility by four- to fivefold concomitant with a decrease in intra-ocular pressure (IOP). Since there are great differences in the anatomy of the aqueous outflow routes between cats and primates, we have examined the effects of CGRP in the cynomolgus monkey. The possible influence of the sensory neuropeptides cholecystokinin (CCK), galanin and substance P on the outflow facility and IOP were also investigated. Determinations were performed using a two-level constant-pressure procedure. At 40–60 min after intracameral injection of 3 μg CGRP the outflow facility was increased from 0·68±0·11 to 1·03±0·15 μl min−1 mmHg−1 in the CGRP-treated eyes, and from 0·71±0·12 to 0·79±0·10 μl min−1 mmHg−1 in the control eyes. The mean difference in increase was 0·27±0·06 μl min−1 mmHg−1 (P < 0·01, N = 7). During the experiments there was a small rise in the IOP. CGRP at a dose of 3 μg caused a small rise in aqueous humor protein concentration. An attempt to release endogenous CGRP with capsaicin did not result in an increased outflow facility. Three micrograms each of CCK, galanin and substance P had no significant effect on either the outflow facility or the IOP. A miosis was observed in the experiments with CCK in agreement with previous findings. CCK seems thus to cause contraction of the pupillary sphincter but does not influence the ciliary muscle sufficiently to cause a facility effect in the monkey eye. Our results indicate that the effect of CGRP on the outflow facility in the monkey eye is much smaller than in cats, and that the other sensory neuropeptides tested have no clear effects on the conductance of the outflow routes.
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| 2. |
- Beding-Barnekow, B., et al.
(författare)
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Systemic and intraocular uptake of spantide, a tachykinin antagonist, following topical application to the rabbit eye.
- 1990
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Ingår i: Experimental Eye Research. - 0014-4835. ; 50:1, s. 21-26
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Tidskriftsartikel (refereegranskat)abstract
- Previous observations have indicated that topical application to the rabbit eye of tachykinin antagonists, including spantide, effectively prevents the miosis and the disruption of the blood-aqueous barrier consequent to ocular injury. The present study shows that spantide is taken up into the rabbit eye following topical application. This was established by determination of spantide in the aqueous humor by radioimmunoassay. The concentrations reached in the aqueous humor were those that could be expected to block tachykinin receptors. The elimination of spantide from the aqueous humor was found to be slow. From HPLC analysis it seemed that spantide in the aqueous humor is degraded to smaller products, predominantly spantide 5–11. Some of the topically applied peptide appeared in the general circulation. Here the rate of elimination was rapid by comparison. Very small amounts of spantide appeared in the cerebrospinal fluid after intravenous injection.
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| 3. |
- Andersson, Madeleine, et al.
(författare)
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Decreased caspase-3 activity in human lens epithelium from posterior subcapsular cataracts
- 2003
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Ingår i: Experimental Eye Research. - 0014-4835. ; 76:2, s. 175-82
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Tidskriftsartikel (refereegranskat)abstract
- Apoptosis has been implied in normal lens development in the embryo as well as in lens fibre differentiation. It has also been suggested to play a role in non-congenital cataract and in the formation of posterior subcapsular opacification, but data on the presence of apoptosis in human lens epithelium from cataractous lenses are scarce and conflicting. The present study aimed to investigate apoptosis in lens epithelium from patients undergoing cataract surgery. The amount of apoptosis detected was correlated to age, gender, type of cataract, medications and disease. Moreover, the ability of human lens epithelial cells in culture to respond to the apoptosis-inducing agent staurosporin by activation of caspase-3 was investigated. Human lens capsulotomy specimens were collected immediately after surgery, frozen and later analysed with respect to caspase-3 activity, using the fluorogenic substrate Ac-DEVD-AMC. Generally, the activity of caspase-3 detected in this manner was very low and in 23% of the specimens it was non-detectable. However, there were differences in caspase activity between lens epithelial cells from different types of cataract, where samples from lenses with posterior subcapsular cataract exhibited significantly lower caspase-3 activity than lenses with a clear subcapsular zone. Age, gender or medications did not show any correlation with caspase activity but human capsulotomy specimens from diabetic patients exhibited significantly lower caspase-3 activity. Staurosporin caused a concentration-dependent increase in caspase activity in cultured human lens epithelial cells and the amount of apoptotic nuclei was also increased as viewed by staining with Hoechst 33342, showing chromatin condensation and nuclear fragmentation. Similar results were obtained when fresh human lens capsulotomy specimens were exposed to 1000 nM staurosporin for 24 hr. To conclude, the present data indicate that human lens epithelial cells have the ability to respond to apoptosis-inducing agents with caspase-3 dependent apoptosis, and that even though the general level of apoptosis in human lens epithelium in vivo is low, there are differences in caspase-3 activity levels in lenses with or without posterior subcapsular cataract. The latter finding supports previous studies indicating that this type of cataract may result from defective differentiation, in which apoptosis may play an important role.
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| 4. |
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| 5. |
- Alm, Albert, et al.
(författare)
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Uveoscleral outflow - A review
- 2009
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Ingår i: EXPERIMENTAL EYE RESEARCH. - : Elsevier BV. - 0014-4835 .- 1096-0007. ; 88:4, s. 760-768
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- The uveoscleral outflow route was described more than 40 years ago. Part of aqueous leaves the eye through the iris root. The ciliary muscle, and there are large species differences in the fraction of aqueous outflow that leaves the eye through this route. In non-human primates 40-50% of aqueous leaves the eye by the uveoscleral route. In human eyes most data has been collected by indirect calculations, with results suggesting a similar fraction, at least in eyes from younger individuals. An age-dependent reduction in uveoscleral flow in human eyes may explain the initial difference seen between non-human primate and human eyes. Unlike trabecular outflow, intraocular pressures within the normal range have little effect on uveoscleral outflow. This may be explained by the fact that changes in intraocular pressure have little effect on the pressure gradient for flow through the ciliary muscle, which is likely to be the rate-limiting step in uveoscleral outflow. The state of the ciliary muscle is important and contraction reduces while relaxation increases uveoscleral flow. Similar effects are achieved with cholinergic agonists and antagonists. Epinephrine increases uveoscleral flow, most likely through stimulating beta(2)-adrenergic receptors. Prostaglandin F-2 alpha and prostaglandin F-2 alpha-analogues effectively reduce intraocular pressure by increasing uveoscleral flow. This is mediated by structural changes in the extracellular matrix of the ciliary muscle, and is likely to contribute to a valuable excess route for aqueous and proteins during intraocular inflammation. Whether uveoscleral flow plays a significant role in any other eye disease is not clear. Thus, 40 years later we are able to successfully increase aqueous flow through the uveoscleral route, a valuable contribution to glaucoma treatment, but we still have only a limited understanding on its physiological role.
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| 6. |
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| 7. |
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| 8. |
- Badian, Reza A., et al.
(författare)
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The inferocentral whorl region and its directional patterns in the corneal sub-basal nerve plexus: A review
- 2024
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Ingår i: Experimental Eye Research. - : ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. - 0014-4835 .- 1096-0007. ; 244
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Forskningsöversikt (refereegranskat)abstract
- There has been a growing application of in vivo confocal microscopy (IVCM) in the examination of corneal microstructure, including different corneal layers and corneal nerve fibers in health and in pathological conditions. Corneal nerves forming the sub-basal nerve plexus (SBNP) beneath the corneal basal epithelial cell layer in particular have been intensively researched in health and disease as a marker for corneal neurophysioanatomical and degenerative changes. One intriguing feature in the SBNP that is found inferior to the corneal apex, is a whorl-like pattern (or vortex) of nerves, which represents an anatomical landmark. Evidence has indicated that the architecture of this 'whorl region' is dynamic, changing with time in healthy individuals but also in disease conditions such as in diabetic neuropathy and keratoconus. This review summarizes the known information regarding the characteristics and significance of the whorl region of nerves in the corneal SBNP, as a potential area of high relevance for future disease monitoring and diagnostics.
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| 9. |
- Bakall, Benjamin, et al.
(författare)
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Enhanced accumulation of A2E in individuals homozygous or heterozygous for mutations in BEST1 (VMD2)
- 2007
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Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835 .- 1096-0007. ; 85:1, s. 34-43
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Tidskriftsartikel (refereegranskat)abstract
- Best vitelliform macular dystrophy (BMD) is an autosomal dominant inherited macular degenerative disease caused by mutations in the gene BEST1 (formerly VMD2). Prior reports indicate that BMD is characterized histopathologically by accumulation of lipofuscin in the retinal pigment epithelium (RPE). However, this accumulation has not been quantified and the chemical composition of lipofuscin in BMD has not been examined. In this study we characterize the histopathology of a donor eye from a rare individual homozygous for a mutation (W93C) in BEST1. We find that this individual's disease was not any more severe than has been described for heterozygotes. We then used this tissue to quantify lipofuscin accumulation by enriching intracellular granules from RPE cells on sucrose gradients and counting the granules in each density fraction. Granules from the homozygous donor eye as well as a donor eye from an individual heterozygous for the mutation T6R were compared with age-matched control eyes. Interestingly, the least dense fraction, representing classical lipofuscin granules was either not present or significantly diminished in the BMD donor eyes and the autoflourescence associated with lipofuscin had shifted to denser fractions. However, a substantial enrichment for granules in fractions of higher density was also noted in the BMD samples. Inspection of granules from the homozygous donor eye by electron microscopy revealed a complex abnormal multilobular structure. Analysis of granules by HPLC indicated a 1.6- and fourfold overall increase in A2E in the BMD eyes versus age-matched control eyes, with a shift of A2E to more dense granules in the BMD donor eyes. Despite the increase in A2E and total intracellular granules, the RPE in the homozygous donor eyes was relatively well preserved. Based on these data we conclude that the clinical and histopathologic consequences to the homozygous donor were not any more severe than has been reported previously for individuals who are established or presumptive heterozygotes. We find that A2E is a component of the lipofuscin accumulated in BMD and that it is more abundant than in control eyes suggesting that the etiology of BMD is similar to Stargardt's disease and Stargardt-like macular dystrophy. Finally, the changes we observe in the granules suggest that the histopathology and eventual vision loss associated with BMD may be due to defects in the ability of the RPE to fully degrade phagocytosed photoreceptor outer segments.
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| 10. |
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