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Biomedical subjects

R C Tripathi

Publications and source records attributed to R C Tripathi.

At least 91 records · Page 5Linked to original sources

Effects of dopamine receptor activation on the level of cyclic AMP in the trabecular meshwork.

We examined the effects of dopamine and of a selective DA1 agonist, fenoldopam, on the levels of cyclic AMP in the trabecular meshwork, freshly excised from porcine and canine eyes. As measured by radioimmunoassay, fenoldopam at a concentration of 10(-5) M caused a 4-fold increase in the cyclic AMP content, from a basal level of 24.4 +/- 1.9 to 101.8 +/- 6.3 pmol/mg protein, of the trabecular meshwork samples from porcine eyes. In tissue samples from canine eyes, fenoldopam at a concentration of 10(-4) M increased the endogenous cyclic AMP level from a basal value of 26.0 +/- 4.6 to 64.2 +/- 5.7 pmol/mg protein. Dopamine, although less potent, produced a similar response. Preincubation with a DA1 receptor antagonist, SCH 23390, inhibited the increase in cyclic AMP levels by 90%. Such inhibition did not occur with the alpha- and beta-receptor antagonists phenoxybenzamine and propranolol, respectively. This investigation demonstrates that adenylate cyclase-coupled DA1 receptors are present in porcine and canine trabecular meshwork tissue.

Animals↗

Contact lens-associated Acanthamoeba keratitis: a report from the USA.

Acanthamoeba keratitis is a serious complication of contact lens wear. The majority of reports documented in the literature are from the USA. The typical features of this condition are reported and illustrated by personal observations. Clinically, Acanthamoeba keratitis can be misdiagnosed as viral, especially Herpes simplex, fungal, or bacterial keratitis. Culture and microscopic examination of corneal scrapings, biopsy, or of the disc obtained at keratoplasty, and special staining techniques, including indirect immunofluorescence, can provide the definitive diagnosis. We discuss the medical and surgical management of this disease, as well as the risk factors and preventive measures. Knowledge of the factors which are responsible for the low incidence of contact lens-associated Acanthamoeba keratitis in Europe, would be helpful in understanding the epidemiology of this disease.

Acanthamoeba↗

Retinal tacks: tolerance and tissue reaction in a human eye.

We report the histopathologic findings in a human eye enucleated after insertion of three nonmagnetic, metallic alloy tacks for treatment of a giant retinal detachment. Five months after surgery one of the tacks was detected in the anterior chamber. Two tacks remained in situ and induced a localized glial reaction, breaks in Bruch's membrane, disappearance of the retinal pigment epithelium and choriocapillaris immediately around the tack, and a variable extent of chorioretinal adhesion. The penetration of the tacks in the choroid and sclera was associated with a localized scar and only a mild inflammatory reaction, but all tacks themselves were free of inflammatory cells and degradation. The two tacks remaining in place were tolerated by the posterior segment. After comparing and contrasting our findings with those documented in the rabbit model, we conclude that overcoming dislodgement problems will require improved insertion techniques and tack design.

Anterior Chamber↗

Tissue plasminogen activator in human aqueous humor and its possible therapeutic significance.

By using an enzyme-linked immunosorbent assay, we detected a significant amount of tissue plasminogen activator (0.8 +/- 0.17 ng/ml) in the aqueous humor of ten normal human eyes. It was also identified on Western blot analysis. The ratio of tissue plasminogen activator to total protein in aqueous humor was about 30 times greater than the ratio of tissue plasminogen activator to total protein in plasma. There was evidence that at least some of the tissue plasminogen activator in the aqueous humor was synthesized locally by the structures bordering the anterior chamber of the eye. Tissue plasminogen activator may be a useful therapeutic modality in clinical conditions of delayed dissolution of fibrin in the eye.

Aqueous Humor↗

Effects of selective dopamine-1 receptor activation on intraocular pressure in man.

The lack of specific agonists and antagonists has, until recently, precluded investigation of a role for dopamine receptors in the control of intraocular pressure. In the present study, we have examined the effects of fenoldopam, a novel selective dopamine1 (DA1) receptor agonist, on intraocular pressure, in eight healthy human volunteers. Fenoldopam, infused intravenously at 0.5 micrograms kg-1 min-1, increased intraocular pressure from 14.6 +/- 0.9 to 17.6 +/- 1.4 mmHg (P less than 0.05) while a control saline infusion had no effect. Pupil diameter and blood pressure did not change. In the same subjects, i.v. norepinephrine or angiotensin II both increased intraocular pressure--from 13.8 +/- 1.4- to 17.6 +/- 1.4 mmHg and from 13.4 +/- 1.3- to 17.5 +/- 1.7 mmHg respectively (P less than 0.05), and mean arterial pressure by about 20 mmHg. These data suggest that: (1) DA1 receptor activation can modulate intraocular pressure; (2) the intraocular pressure effects of the DA1 receptor agonist, fenoldopam, are independent of changes in systemic blood pressure, in contrast to those of norepinephrine or angiotensin II where intraocular and systemic blood pressures increase in parallel; (3) the ability of a DA1 receptor antagonist to lower intraocular pressure merits investigation.

Adolescent↗

Tissue plasminogen activator in the lens.

Biochemical analyses of normal lenses from monkey, dog and calf eyes revealed significant levels of tissue plasminogen activator (t-PA). By immunohistochemistry, a positive reaction product for t-PA was seen, in descending order of staining intensity, in the central epithelium, equatorial epithelium, superficial fibers of the anterior cortex, and anterior capsule of both human and monkey lenses. The possible functions of t-PA in the normal 801s include regulation of deformation that occurs in the anterior lens epithelium and fibers during the process of accommodation, and the destructive remodeling of the extracellular matrix including the lens capsule.

Animals↗

Multiple dosing of prostaglandin F2 alpha or epinephrine on cynomolgus monkey eyes. III. Histopathology.

Prostaglandins (PGs), or their derivatives, are potent ocular hypotensive agents which may prove useful in glaucoma therapy. PGF2 alpha (250 micrograms in 50 microliter saline) or epinephrine 2% solution (50 microliter) was topically applied twice daily for 2 weeks to one eye of six cynomolgus monkeys for each agent. Contralateral control eyes received their respective vehicles. By light microscopy, there was no evidence of inflammation, corneal changes, retinal pathology (including cystoid macular edema), or other adverse effects. Likewise, by electron microscopy of the peripheral cornea, anterior chamber angle, iris base and ciliary body, no differences were noted between treated and control eyes. Therefore, multiple dosing with PGF2 alpha in subhuman primate eyes did not result in notable histopathological changes that would contraindicate a clinical trial in glaucoma patients.

Animals↗

Acanthamoeba keratitis and infectious crystalline keratopathy.

Two cases of Acanthamoeba keratitis and infectious crystalline keratopathy, occurring simultaneously, are presented. Three and 12 months after initiating topical corticosteroid therapy in cases 1 and 2, respectively, alpha-hemolytic Streptococcus viridans was cultured from each cornea. Topical corticosteroid therapy was initiated for the treatment of an annular stromal opacity, presumably secondary to herpes simplex keratitis. Acanthamoeba was identified in culture following penetrating keratoplasty in case 1, and Acanthamoeba polyphaga, Acanthamoeba rhysodes, and Acanthamoeba castellanii were identified using indirect fluorescent antibody staining in case 2. Histopathologic examination and electron microscopy demonstrated sheets of cocci within stromal lamellae characteristic of infectious crystalline keratopathy and double-walled encysted organisms typical of Acanthamoeba. These case reports alert one to the possibility of developing bacterial keratitis, such as infectious crystalline keratopathy, following the use of topical corticosteroids for the treatment of Acanthamoeba keratitis.

Adrenal Cortex Hormones↗

Localization of sialic acid moieties in the endothelial lining of Schlemm's canal in normal and glaucomatous eyes.

The distribution of sialic acid moieties in the trabecular wall of Schlemm's canal in normal human and monkey eyes, as well as in limited tissue samples from patients with primary open-angle glaucoma (POAG), was investigated by using polycationic ferritin (PCF) at varying pH and colloidal iron at pH 1.8. At pH 1.8-1.9, both PCF and colloidal iron labeled the luminal surface of the endothelial cells of Schlemm's canal in normotensive monkey and human eyes, whereas binding was sparse and random on the basal surface. At a pH of 3.3 and higher, PCF showed increased binding that was confirmed exclusively to the luminal surface of the cells. In trabeculectomy tissue samples from eyes with POAG, PCF at pH 1.9 showed a greater density of labeling on both the basal and luminal cell surfaces, as well as in the subendothelial region, than was observed in normotensive eyes. Given the fact that sialic acid is a moiety which stabilizes cell membranes, we suggest that in normal eyes the absence of sialated molecules on the basal cell surface leaves 'receptor' sites for the initiation of the macrovacuolation process which allows the bulk outflow of aqueous humor across the endothelial barrier of Schlemm's canal. Our preliminary observations in glaucomatous eyes indicate a loss of such receptor sites, which may account for the depletion of macrovacuolar configurations in cases of advanced POAG. Our discussion relates these findings to the pathogenesis of POAG and to the possible role for a defective transmembrane interaction of the surface glycoproteins (fibronectin and laminin) with the cytoskeleton of the endothelial cells lining Schlemm's canal and the cells in the pericanalicular tissue.

Adult↗

Tissue plasminogen activator in avascular tissues of the eye: a quantitative study of its activity in the cornea, lens, and aqueous and vitreous humors of dog, calf, and monkey.

We analysed the tissue plasminogen activator (TPA) content of the corneal epithelium, endothelium, and stroma and of the lens, as well as the aqueous and vitreous humors, in dog, calf, and monkey eyes. A quantitative estimation of the TPA activity in the corneal tissues by the [125I]fibrin-coated well assay showed similar levels of activity in the corneal epithelium, stroma, and endothelium. However, some differences were observed among the three mammalian species analysed. The values, expressed in urokinase (UK) units of activity per mg protein, ranged from 0.8 +/- 0.22 to 1.03 +/- 0.23 for the epithelium, 0.47 +/- 0.13 to 0.98 +/- 0.2 for the stroma, and 0.48 +/- 0.11 to 0.93 +/- 0.22 for the endothelium. The lens, the vitreous and the aqueous humor yielded low to negligible values. However, by using the enzyme-linked immunosorbent assay (ELISA) method, we detected an appreciable amount of TPA in the lens (9.49 +/- 1.5 ng TPA per ml lens), corneal epithelium (1.43 +/- 0.29 ng TPA per mg protein) and vitreous humor of the dog (5.71 +/- 0.61 ng TPA per ml vitreous humor) and of the calf (5.7 +/- 0.44 ng TPA per ml vitreous humor). Such discrepancies may reflect species-specific variation in the TPA content of the tissues and possibly the limitations of the techniques utilized, because of the problem related to cross-reactivity between the TPA of a given species and the antibody used in the assays.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Age-related changes in protein profiles of the normal human trabecular meshwork.

The protein profile of the trabecular meshwork from 44 normal human eyes of various ages, ranging from 5 months to 87 years, was investigated by using sodium dodecyl sulfate-polyacrylamide-gel (SDS-PAGE) electrophoresis and a highly sensitive silver-stain technique. Samples from each eye were analysed individually to avoid anomalies that may occur with tissue pooling. More than 20 protein bands were consistently visible at all ages and varied in molecular weight from 20,000 to 290,000 MW. The shifts which occurred in band prominence with increasing age included a consistent decrease in the intensity of bands at MWs 42,000 (tentatively identified as G-actin) and 58,000; a noticeable increase in the intensity of the bands at MWs 140,000 and 160,000 that correspond to alpha I and II components of type IV collagen; and a gradual disappearance of a faint band at MW 68,000 in eyes older than 31 years. Our study shows that molecular aging does occur in the trabecular meshwork. The data presented also provides a basis for comparison of the polypeptide alterations that may occur in primary open-angle glaucoma and in other disease processes.

Adolescent↗

Distribution of tissue plasminogen activator in human and monkey eyes. An immunohistochemical study.

The authors examined various structures of human and rhesus monkey eyes for the presence of tissue plasminogen activator (t-PA) by using the peroxidase-antiperoxidase immunohistochemical technique with a monoclonal antibody specific for human t-PA. Positive staining for t-PA was observed both intracellularly and in the extracellular matrix of many tissues in both species. The tissues which stained intensely for t-PA included the corneal endothelium, corneal epithelium, trabecular meshwork, lens epithelium, peripheral vitreous, uveal tract, inner retina, and all vascular endothelia. The apparent minor difference in staining intensity between human and monkey eyes may be related to the time-dependent degradation of t-PA, to variations in the tissue content of t-PA, or to the difference in animal species. The discussion includes a consideration of the fibrinolytic activity of t-PA and of its emerging role in the destructive remodeling of the extracellular matrix in various ocular structures.

Animals↗

Tissue plasminogen activator in the trabecular endothelium.

By quantitative analysis of tissue plasminogen activator (TPA) in the trabecular endothelium, corneal endothelium, and iris in the eyes of monkeys and dogs, we found significant levels of TPA activity. In a [125I]fibrin-coated well assay, the levels for the dog and monkey were, respectively: trabecular endothelium, 0.2 and 0.5; corneal endothelium, 0.8 and 0.5 IU per mg protein. The iris tissue showed high TPA activity, but its protein content could not be measured with the techniques employed. Activity in the aqueous humor was not detectable. By the ELISA technique, the values (in ng TPA/mg tissue protein) for the dog and monkey were, respectively: trabecular endothelium, 0.16 and 0.44; corneal endothelium, 0.48 and 0.92. Again, iris tissue showed high TPA activity, whereas the aqueous humor showed low activity (0.86 ng/ml). The data obtained with the two methods showed a reasonable consistency, although a direct comparison was not possible because two separate standards were used. The presence of TPA in the trabecular endothelium, corneal endothelium, and iris may be important in modulating the resistance to aqueous outflow under normal conditions as well as those of hyphema.

Animals↗

Anomalies of retinal architecture in Aicardi syndrome.

Eyes obtained at autopsy from a female infant with Aicardi syndrome (chorioretinal lacunae, agenesis of the corpus callosum, and seizures) were studied by light and electron microscopy. The retinal insertion was displaced anteriorly over the ciliary body, the choroid was attenuated, and the retinal pigment epithelium showed hyperplasia and pigment migration throughout the sensory retina. Rosettes of photoreceptorlike cells and inversion of the photoreceptor layer were found. A hole within a lacuna showed total absence of the sensory retina. Optic disc epipapillary tissue consisted of glial and fibrous elements with a vascular core. The mechanism of photoreceptor folding is considered. The continuity of the external limiting membrane with the retinal pigment epithelium at sites of photoreceptor folding seen in our case suggests defective early development.

Agenesis of Corpus Callosum↗

Pathogenesis of cataracts in patients with Lowe's syndrome.

Based on our morphologic and ultrastructural studies, we suggest that the characteristic lens opacities in Lowe's syndrome result from a genetic defect in the lens cells. This defect manifests early in embryogenesis, and the progression of the lens opacities is related to both the inherent genetic abnormality and the prevailing extralenticular environment. The defective formation and subsequent degeneration of the primary posterior lens fibers account for their loss and for the flattened, discoid, or ring-shaped cataract. The other findings, such as anterior polar cataract, subcapsular fibrous plaque, capsular excrescences, bladder cells, and posterior lenticonus are not necessarily specific for Lowe's syndrome. We believe that the pathogenesis of Lowe's cataract can be explained by Lyon's hypothesis, which implies that, very early in embryogenesis (at the stage of the primitive streak), one of the two X chromosomes in females is deactivated. We consider the high incidence of lens opacities in female carriers to be due to this random deactivation. In male probands, however, all lens cells are affected, since there is no normal X chromosome to nullify the effect of the Lowe gene.

Cataract↗

Lenticular opacities in carriers of Lowe's syndrome.

Eleven possible and five obligate carriers of Lowe's syndrome from the same pedigree were examined for lens opacities. All of the obligate carriers and 4 of the 11 at risk had lens abnormalities. The lenticular abnormalities consisted of cortical dots of various shapes that increased in number with the age of the carriers in older obligate carriers, subcapsular plaques were common. Because the syndrome is X linked, such lens changes are explainable by the Lyon's hypothesis. When the number of opacities seen in these subjects were compared to those seen in 100 normal control females 10 to 20 years of age, cataractagenic cases such as diabetes, Down's and fetal nuclear opacities excluded, four probable carriers were identified among the eleven possible carriers in the pedigree. These subjects had significantly greater numbers of opacities, similar to those seen in obligate carriers, compared to controls. We conclude that progressive lens changes are present in carriers of Lowe's syndrome and that young carrier females can be identified reliably when they are compared to age-matched controls by modifying the grading system of Brown and Gardner.

Adolescent↗