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Biomedical subjects

T W Gardner

Publications and source records attributed to T W Gardner.

At least 37 records · Page 2Linked to original sources
PubMed1997

Physiological transport properties of cultured retinal microvascular endothelial cell monolayers.

PURPOSE: To characterize baseline transport properties: hydraulic conductivity (Lp), albumin permeability (Pe), and transendothelial electrical resistance (TER) of bovine retinal microvascular endothelial cells (RMEC) in the development of an in vitro model of the blood-retinal barrier (BRB). METHODS: RMEC were grown on porous, polycarbonate filters for determination of the number of days required to achieve minimal transport rates. Lp, Pe, and TER were measured by utilizing a bubble tracking spectrophotometer, by quantifying the diffusional movement of fluorescein isothiocyanate-labeled albumin, and by utilizing a Millipore electrical resistance meter, respectively. RESULTS: Lp decreased significantly from 7.82 +/- 0.85 x 10(-7) (mean +/- SEM) cm/sec/cm H2O at post-plating Day 5 to 1.44 +/- 0.26 x 10(-7) cm/sec/cm H2O at Day 9. Pe of the monolayer also decreased progressively with days post-plating from 3.44 +/- 0.53 x 10(-6) cm/sec at Day 7 to a minimum of 1.95 +/- 0.29 x 10(-6) cm/sec at Day II. Peak TER fluctuated until Day 7, when it began to steadily increase from 17.14 ohm-cm2 to a peak value of 25.42 ohm-cm2 at Day 10, decreasing from then on to 22.24 ohm.cm2 on Day 12. Known disrupters of the BRB, NECA and VEGF, elicited significant increase in RMEC Lp showing the sensitivity of this model to pharmacological alterations. CONCLUSIONS: Our data indicate that RMEC grown on polycarbonate filters form a restrictive monolayer of cells, which exhibit dynamic alterations in response to pharmacological agents, thus demonstrating an in vitro model of the BRB. Future studies with the model may offer insights into the pathogenesis of retinal vascular diseases and allow convenient testing of pharmacological interventions.

Adenosine↗
PubMed1997

Astrocytes increase barrier properties and ZO-1 expression in retinal vascular endothelial cells.

PURPOSE: Diabetic retinopathy and other diseases associated with retinal edema are characterized by increased microvascular leakage. Astrocytes have been proposed to maintain endothelial function in the brain, suggesting that glial impairment may underlie the development of retinal edema. The purpose of this study was to test the effects of astrocytes on barrier properties in retinal microvascular endothelial cells. METHODS: Bovine retinal microvascular endothelial cells were exposed to conditioned media from rat brain astrocytes. Transendothelial electrical resistance (TER) was determined on 24-mm Transwell (Cambridge, MA) polycarbonate filters with the End-Ohm device (World Precision Instruments, Sarasota, FL). ZO-1 protein content was quantified by microtiter enzyme-linked immunosorbent assay. RESULTS: Astrocyte-conditioned medium (ACM) significantly increased TER (P < 0.0001) and ZO-1 content (P < 0.01). Both serum-containing and serum-free N1B defined ACM increased ZO-1 expression, but heating abolished the effect. Serum-free ACM decreased cell proliferation by 16%. CONCLUSIONS: Astrocytes release soluble, heat-labile factors that increase barrier properties and tight junction protein content. These results suggest that astrocytes enhance blood-retinal barrier properties, at least in part by increasing tight junction protein expression. Our findings suggest that glial malfunction plays an important role in the pathogenesis of vasogenic retinal edema.

Animals↗
PubMed1996

Histamine reduces ZO-1 tight-junction protein expression in cultured retinal microvascular endothelial cells.

We examined ZO-1 protein content in cultured retinal vascular endothelial cells to test the hypothesis that histamine alters tight-junction-protein expression. Histamine (10(-9) -10(-4) M) causes a reversible concentration-dependent reduction of ZO-1 protein content, mediated by both H1 and H2 receptors. Histamine reduces ZO-1 expression within the time associated with increased paracellular permeability. Tight-junction-protein alterations may be a novel explanation for the mechanism by which vasoactive agents increase microvascular permeability.

Animals↗
PubMed1996

Central serous chorioretinopathy in women.

BACKGROUND: Central serous chorioretinopathy is a disorder that typically affects young and middle-aged men. Although extensive information is available pertaining to the clinical features of central serous chorioretinopathy in men, little is known about this condition in women. MATERIALS AND METHODS: The authors reviewed the medical records and photographic files of women who received a diagnosis of central serous chorioretinopathy. The women were divided into three groups for data analysis: idiopathic, exogenous corticosteroid use, and pregnancy. RESULTS: Fifty-one women with active central serous chorioretinopathy were evaluated. These findings in women with idiopathic serous chorioretinopathy were similar to those described in men, with the exception that women tend to be older at the time of onset. Central serous chorioretinopathy in women taking exogenous corticosteroids more likely was characterized by bilateral involvement and subretinal fibrin. Central serous chorioretinopathy in pregnant women typically developed in the third trimester and resolved spontaneously within 1-2 months after delivery. CONCLUSION: Idiopathic central serous chorioretinopathy is similar in women and men, with the exception that women tend to be more older at the time of onset. The finding of exogenous corticosteroid use in a significant number of women in our study provides further support that cortisol may play a role in the development of central serous chorioretinopathy. The mechanism by which cortisol influences the development of central serous chorioretinopathy is unclear.

Adrenal Cortex Hormones↗
PubMed1995

Digoxin does not accelerate progression of diabetic retinopathy.

OBJECTIVE: To test the hypothesis that digoxin, an inhibitor of Na(+)-K(+)-ATPase activity, accelerates the progression of diabetic retinopathy. RESEARCH DESIGN AND METHODS: We compared the incidence and risk of retinopathy in 120 digoxin-taking vs. 867 non-digoxin-taking diabetic participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) and in 117 digoxin-taking vs. 1,883 non-digoxin-taking diabetic subjects in the Early Treatment Diabetic Retinopathy Study (ETDRS). In both studies, retinopathy was detected by grading stereoscopic color photographs using the modified Airlie House classification scheme, and a two-step difference in baseline retinopathy grade was considered significant. RESULTS: After controlling for other risk factors, we found no statistically significant association with either 4-year incidence of retinopathy (WESDR) or progression of retinopathy (WESDR and ETDRS) in patients taking digoxin at baseline compared with those not taking digoxin. CONCLUSIONS: These data suggest that digoxin therapy does not adversely affect the course of diabetic retinopathy.

Adult↗
PubMed1995

Antihistamines reduce blood-retinal barrier permeability in type I (insulin-dependent) diabetic patients with nonproliferative retinopathy. A pilot study.

PURPOSE: To determine if histamine receptor stimulation mediates increased blood-retinal barrier (BRB) permeability in patients with diabetic retinopathy, as it does in experimental diabetes. METHODS: Fourteen patients with type I (insulin-dependent) diabetes and mild nonproliferative diabetic retinopathy were treated with combined astemizole, 20 mg, and ranitidine, 600 mg, or an identical placebo for 6 months in a double-masked fashion. Blood-retinal barrier permeability was measured by vitreous fluorometry at baseline and at 3 and 6 months. RESULTS: Permeability was significantly reduced in the group treated with antihistamines (P < 0.05) compared with the placebo group. There were no concomitant significant changes in systemic arterial blood pressure or HbA1c values. CONCLUSION: These pilot data suggest that histamine receptors influence permeability of the BRB in human diabetes. Further studies of the effects of antihistamines on diabetic retinopathy are warranted.

Adult↗
PubMed1995

Histamine, ZO-1 and increased blood-retinal barrier permeability in diabetic retinopathy.

PURPOSES: First, to develop an improved retinal capillary endothelial cell culture system which exhibits some of the physiologic features of the bloodretinal barrier; second, to use this model to determine how histamine and chemical conditions of diabetes effect expression of the tight junction protein, ZO-1; and third, to discuss application of the Henle-Koch postulates to the problem of diabetic retinopathy. METHODS: Bovine retinal capillary endothelial cells were exposed to varying serum and growth factor concentrations, as well as astrocyte-conditioned medium, in order to establish a model of the blood-retinal barrier. Cells were also exposed to varying concentrations of histamine, and of insulin and glucose. The expression of ZO-1 tight junction protein was determined by immunocytochemistry and immunoblotting. RESULTS: Modified concentrations of growth factors reduced endothelial cell proliferation, without reducing viability. Astrocyte conditioned medium increased ZO-1 protein content. Histamine reduced ZO-1 protein content. Both high glucose (20mM) and low insulin (10(-12)M) reduced ZO-1 protein content compared to control conditions (5mM glucose and 10(-9) M insulin). CONCLUSIONS: Control of culture conditions results in a more physiologic in vitro model of the blood-retinal barrier. Soluble factors from astrocytes promote tight junction formation. Both histamine and chemical conditions of diabetes diminish tight junction formation. These factors may mediate blood-retinal barrier breakdown in diabetic retinopathy. Henle-Koch postulates for diabetic retinopathy are presented.

Animals↗
PubMed1993

Current patterns of intraocular gas use in North America.

A 1987 survey of 365 members of the Retina and Vitreous societies revealed that use of long-acting intraocular gases was both widespread and frequent. However, despite the expanded use of intravitreal gases and the stated intention of the Food and Drug Administration to approve premarket applications for use of sulfur hexafluoride and perfluoropropane, there are still limitations in the ready availability of these substances. Therefore, we conducted another survey to determine current patterns of intraocular gas use. The results indicate that more surgeons are using long-acting gases. The data also demonstrate the selective use of pneumatic retinopexy with geographic pockets of increased retinopexy use in California and Florida. Finally, 100% of respondents now indicate that they consider the use of sulfur hexafluoride and perfluoropropane to be a standard of care.

Air↗
PubMed1993

Intraocular pressure fluctuations during scleral buckling surgery.

PURPOSE: The purposes of this study are to measure real-time intraocular pressure (IOP) during scleral buckling and to determine the effects of elevated IOPs on ocular perfusion. PATIENTS AND METHODS: A standard 4-mm, 20-gauge infusion cannula was inserted through the pars plana, connected to a standard hemodynamic monitoring unit with an electronic pressure transducer, and calibrated. The authors measured real-time IOP in 20 eyes undergoing scleral buckling surgery for primary rhegmatogenous retinal detachments and determined the IOP required to close the central retinal artery. Pressure measurements were read from the monitor videoscreen intraoperatively and from a continuous paper tracing postoperatively. RESULTS: The patients ranged in age from 24 to 88 years (mean, 59.7 years). The highest IOP elevations occurred during scleral depression and cryopexy, ranging up to 210 mmHg (mean, 116 mmHg). Pressures at which the central retinal artery closed ranged from 48 to 110 mmHg (mean, 79.2 mmHg). Manipulations of the globes caused IOPs greater than the central retinal artery perfusion pressures in 13 of the 20 patients. The duration of pressures in excess of the central retinal artery perfusion pressure ranged from 6 to 402 seconds (mean, 118.8 seconds). There were no intraoperative or postoperative complications from the infusion cannula. CONCLUSIONS: Conventional scleral buckling surgery causes wide fluctuations in IOP and may impair ocular perfusion. Additional studies are needed to determine the long-term consequences of these pressure elevations.

Adult↗
PubMed1992

A survey of intraocular silicone oil use in the United States.

PURPOSE: This survey was conducted to determine the pattern of usage of intravitreal silicone oil in the United States. METHODS: A questionnaire was sent to 542 members of the Retina and Vitreous Societies in December 1990, and again 6 weeks later in an attempt to improve the response rate. RESULTS: Two hundred eighty-seven questionnaires (53%) were returned. Ninety-eight percent of the respondents perform vitreous surgery, and 61% of them use silicone oil. This survey determined the degree of participation in Food and Drug Administration (FDA)- and institutional review board-approved protocols and the most common indications for use of silicone oil. Ninety-six percent of the respondents indicated that the use of silicone oil represented an acceptable standard of care. CONCLUSION: Silicone oil is widely used in the United States despite its lack of FDA approval.

Drug Utilization↗
PubMed1991

Reduction of severe macular edema in eyes with poor vision after panretinal photocoagulation for proliferative diabetic retinopathy.

Currently available data from multicenter randomized trials on laser treatment of diabetic macular edema refer only to eyes with pretreatment visual acuities of 20/160 or better. After observing reduction of more severe macular edema and visual improvement following panretinal photocoagulation (PRP) alone in some patients, we reviewed our experience with this problem. In 18 eyes of 14 patients with proliferative diabetic retinopathy and visual acuity of 20/200 or worse, secondary to severe macular edema were identified. At 6 months after PRP without focal macular laser treatment, macular edema was reduced in 13 eyes, 8 of which improved by greater than or equal to 2 lines of vision. Among the latter 8 eyes, the visual acuity of 4 recovered to 20/80 or better; the remaining 10 eyes, which had chronic retinal pigment epithelial atrophy or extensive macular ischemia, did not improve. Based on these observations, we suggest that peripheral PRP performed in multiple sessions over several months may have a beneficial effect on severe macular edema in some eyes with adequate macular perfusion.

Adult↗
PubMed1990

Incorporating safety concerns into design and construction.

The nursing facility industry has provided a high level of fire safety according to statistics from the NFPA. To keep and improve this record, fire safety in the design and construction of nursing facilities must be a priority. Since the ground work of fire safety is laid in the design phase and finalized in the construction phase, such a priority will help lower initial and operating costs, improve the function of the facility, and provide a fire safe environment for residents and staff.

Accident Prevention↗
PubMed1989

Histamine H1 receptors mediate increased blood-retinal barrier permeability in experimental diabetes.

To test the hypothesis that histamine receptors mediate increased blood-retinal barrier permeability in experimental diabetes, 51 rats were made diabetic by streptozocin injection (65 mg/kg; jugular vein) and were held for four weeks. The seven animal groups were as follows: untreated controls; untreated diabetic rats; diabetic rats receiving diphenhydramine hydrochloride (Benadryl); diabetic rats receiving cimetidine hydrochloride (Tagamet); diabetic rats receiving diphenhydramine and cimetidine; diabetic rats receiving purified pork insulin (Iletin II); and diabetic rats receiving insulin and diphenhydramine. All treatments were given during the last week. Blood-retinal barrier permeability was assessed through measurement of the vitreous content of fluorescein isothiocyanate conjugated to bovine serum albumin (FITCBSA) after 20 minutes of FITCBSA circulation. Vitreous FITCBSA content of the diabetic group was 64% greater than control content. Diabetic rats treated with either diphenhydramine or diphenhydramine and insulin had respective decreases of 43% and 40% in vitreous FITCBSA content. The vitreous content of the diabetic group receiving insulin was lowered 37% below untreated diabetic values, while the vitreous FITCBSA content of the diabetic group receiving both insulin and diphenhydramine was reduced 63%. These data indicate that retinal histamine H1-receptor activation may be partially responsible for initial blood-retinal barrier leakage of macromolecules into the vitreous and that this abnormal leakage can be prevented both by diphenhydramine and by insulin. Histamine H1 receptors may play an important role in mediating increased blood-retinal barrier permeability in experimental diabetes.

Animals↗