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Biomedical subjects

E de Juan

Publications and source records attributed to E de Juan.

At least 19 recordsLinked to original sources

Retinal oxygenation and laser treatment in patients with diabetic retinopathy.

The oxygen tension in the preretinal vitreous cavity was measured in human patients undergoing vitreous operations for proliferative diabetic retinopathy. The oxygen tension was significantly higher (P = .004) over areas of retina that had been treated with panretinal photocoagulation than it was over untreated areas in the same retina. This confirmed previous results in animals that showed that panretinal photocoagulation increases the inner retinal oxygen tension. We concluded that panretinal photocoagulation improves the oxygen supply to the inner retina and thereby minimizes the influence of retinal ischemia in diabetic retinopathy.

Blood Pressure

Blood-retinal barrier breakdown caused by diode vs argon laser endophotocoagulation.

We compared the effects of argon and diode laser endophotocoagulation on blood-retinal barrier breakdown using real-time magnetic resonance imaging following intravenous gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) injection. Endophotocoagulation was performed on eyes of pigmented rabbits with either the argon or the diode laser to produce ophthalmoscopically similar lesions. Magnetic resonance imaging studies were performed either 2 or 7 days after laser treatment, and coronal T1-weighted proton images were obtained in the first 20 minutes following Gd-DTPA injection. The mean signal intensity over a region of interest in the vitreous cavity was analyzed, and an initial rate analysis was performed on each time-course curve. Two days after treatment, argon laser-treated eyes showed significantly greater leakage of Gd-DTPA than diode laser-treated eyes. The leakage in both groups was substantially reduced by posttreatment day 7. Histopathologic examination performed 2 days following photocoagulation showed less damage of the retinal pigment epithelium and more severe occlusion of the choriocapillaris and deep choroidal vessels in diode laser-treated eyes. These changes may serve to explain the observed differences in Gd-DTPA leakage.

Animals

Transmission electron microscopic study of a subretinal choroidal neovascular membrane due to age-related macular degeneration.

From a patient with age-related macular degeneration we studied ultrastructurally a disciform scar that was removed from an eye with a vitreous hemorrhage. In cross section, the scar was divided by a retinal pigment epithelial (RPE) cell layer. The choroidal side consisted of fibrovascular tissue with active neovascular buds and inflammatory cells, including macrophages attached to the RPE basement membrane. Apart from the RPE, no components of Bruch's membrane could be identified. The retinal side contained organizing hemorrhage and a collagenous matrix with fibroblastlike cells probably of RPE and choroidal origin. The anatomy and the clinical findings at surgery suggest that such scars lie on (rather than within) the inner collagenous layer of Bruch's membrane and contain two components divided by the original RPE layer. The choroidal side is fibrovascular, including active neovascularization, and the retinal side is fibrous and formed by metaplastic RPE cells and choroidal fibrovascular ingrowth.

Aged

Treatment with intravitreal steroid reduces blood-retinal barrier breakdown due to retinal photocoagulation.

The effect of corticosteroid treatment on blood-retinal barrier breakdown caused by argon-laser panretinal photocoagulation was evaluated in the rabbit eye. One day before photocoagulation, eyes were given either a sub-Tenon (20-mg) or intravitreal (2-mg) injection of triamcinolone acetonide. The severity of blood-retinal barrier breakdown was measured after photocoagulation using rapid sequential magnetic resonance imaging following intravenous administration of gadolinium diethylenetriaminepentaacetic acid. Leakage of gadolinium diethylenetriaminepentaacetic acid into the vitreous space was significantly lower in eyes that received intravitreal triamcinolone acetonide than in control eyes (P = .007); however, sub-Tenon triamcinolone acetonide produced no significant reduction in leakage (P = .65) compared with controls. Fluorescein angiography supported the magnetic resonance imaging findings. We conclude that retinal photocoagulation in the rabbit eye produces blood-retinal barrier breakdown that is partially amenable to corticosteroid treatment.

Animals

Morphometric analysis of macular photoreceptors and ganglion cells in retinas with retinitis pigmentosa.

There have been a number of histopathologic studies of retinas that were taken post mortem from patients with retinitis pigmentosa (RP), but few have addressed the question of transneuronal degeneration of ganglion cells secondary to photoreceptor death. We studied sectioned maculae that were obtained from 41 patients with different genetic forms of RP: autosomal dominant (n = 11); X-linked (n = 9); and simplex (n = 21). We also studied sectioned maculae that were taken from 20 age-matched normal subjects. We counted cell bodies in the photoreceptor and ganglion cell layers at 100-microns (0.35 degrees) intervals from the foveola to 1500-microns eccentricity and compared the mean cell counts among each group with RP. Each RP type had significantly fewer (P < .05) photoreceptors than those of the control group at each 100-microns interval. At eccentricities of 700 to 1500 microns, the retinas with X-linked and autosomal dominant RP had significantly fewer (P < .05) ganglion cells than those of the control group; the simplex RP mean ganglion cell counts were significantly lower (P < .05) than those of the control group, from 1000 to 1500 microns. The mean photoreceptor and ganglion cell counts had a .43 correlation (P < .001) in the zone of 700 to 1500 microns, consistent with transneuronal ganglion cell degeneration. Current experimental attempts to restore vision in diseased retinas by simulating or replacing photoreceptors are based on the premise that ganglion cells are retained after photoreceptor death. Our findings support this assumption.

Adolescent

Oxygen-induced mitochondrial damage and aging.

Although the views of Harman and Gerschman provide a reasonable explanation for many of the effects of aging, they fail to explain why many cell types, from amoebae to mammalian spermatogonia, do not show a time-related involution, while other cells (especially the neurons) change with age. We feel that a better understanding of senescence (from the molecular to the organ and organismic levels) can be gained by integrating the free radical theory of aging with the classic concepts of Minot and Pearl on the role of cell differentiation and metabolic rate in, respectively, triggering and pacing senescence. In agreement with the above, we maintain that aging is the non-programmed but unavoidable "side effect" of oxy-radical damage to the membrane and genome of the mitochondria of irreversibly differentiated cells. If oxy-radical damage to mtDNA occurs, it will block the rejuvenation of the mitochondrial population by the process of organelle division, thus leading to bioenergetic decline and cellular death.

Aging

Scleral buckling surgery for stage 4B retinopathy of prematurity.

Results of scleral buckling in 15 consecutive eyes of 13 infants with stage 4B retinopathy of prematurity (ROP) were reviewed. Ten of 15 retinas achieved macular reattachment with a single scleral buckling procedure. Four of 15 retinas unable to be attached by scleral buckling were reattached after the addition of a single vitreous operation. One of 15 retinas was unable to be reattached despite both a scleral buckling and a single vitreous procedure. Despite macular attachment in all except one eye, visual results were disappointing. Fix and follow visual acuity was present in 3 eyes, light perception in 11 eyes, and no light perception in 1 eye. Average follow-up was 10 months. Possible causes for poor visual outcomes despite retinal reattachment include retinal abnormalities as a result of detachment and amblyopia.

Female

Accurate and precise measurement of blood-retinal barrier breakdown using dynamic Gd-DTPA MRI.

Dynamic T1-weighted magnetic resonance imaging (MRI) after the injection of Gd-DTPA is a promising method for investigating breakdown of the blood-retinal barrier (BRB). Previously, the authors demonstrated that in a T1-weighted image, the initial rate of change in the vitreous water MRI signal as gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enters the vitreous space strongly correlated with the extent of BRB breakdown. Here, a practical approach to measuring a more relevant physiologic parameter is presented: the permeability surface area product (PS). The theory is a development of earlier work used in investigating the breakdown of the blood-brain barrier. The accuracy and precision of this approach was investigated in rabbits pretreated with sodium iodate (30 mg/kg intravenously). The MRI-derived PS normalized to the area of leaky retina (5.65 +/- 0.25 x 10(-4) cm/min, mean +/- standard error of the mean; n = 6) was compared to a similarly normalized PS calculated using a classical physiologic method (4.12 +/- 0.73 x 10(-4) cm/min; n = 6). Good agreement between the two methods was found (P = 0.09). This result demonstrates that the MRI-derived PS is an accurate and precise measure of BRB breakdown under these conditions. The mathematical model of Gd-DTPA distribution in vivo also is validated. Based on these results, several potential sources of error are discussed, including the effect of back-flow of Gd-DTPA from the vitreous space to the plasma, the underlying vascular patency, and MRI slice selection.

Animals

In vivo imaging of breakdown of the inner and outer blood-retinal barriers.

Real-time contrast-enhanced magnetic resonance imaging (MRI) was used to distinguish between experimentally induced breakdown of the vascular (inner) and retinal pigment epithelial (RPE; outer) blood-retinal barrier (BRB) in vivo. Pigmented rabbits were treated with intravenous sodium iodate 30 mg/kg, (a specific RPE cell poison), intravitreal N-ethylcarboxamidoadenosine (NECA) 10(-3) mol/l (which specifically disrupts the vascular BRB), or retinal diode laser photocoagulation. Coronal T1-weighted proton images were acquired in a timed sequence after intravenous injection of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Images were analyzed to localize leakage of Gd-DTPA and determine the permeability surface area product normalized per unit area (PS). The pattern of enhancement observed in eyes treated with sodium iodate differed clearly from that in eyes treated with NECA. PS' values were significantly higher in eyes treated with sodium iodate than with NECA. Simultaneous leakage from the outer and inner BRB in eyes treated with dense retinal laser photocoagulation could be localized and quantitated independently.

Adenosine

Ultrastructural study of Norrie's disease.

We studied the clinicopathologic and ultrastructural features of a full-term infant with Norrie's disease. The infant had bilateral retrolental fibrous vascular masses and retinal detachment with no other apparent physical abnormalities and no family history of ocular defects. A vitrectomy and a membrane peeling were attempted, and specimens of the retina, the retrolental membrane, and a vascularized epiretinal peripheral mass were examined by light and electron microscopy. The retrolental membrane was composed of layered collagenous tissue and contained structures resembling blood vessels. Inner and outer neuroblastic layers were identified in the retinal tissue, but no vessels were present. In the epiretinal mass, portions of retina and cortical vitreous were seen along with primitive vascular structures. The histologic appearance of these specimens suggests that the major pathologic event of Norrie's disease occurs in the retina in the third to fourth gestational month. We believe the subsequent ocular abnormalities found in this patient were secondary to this early retinal malformation and did not represent a progressive ocular disorder.

Abnormalities, Multiple

The management of retinal detachments associated with choroidal colobomas by vitreous surgery.

We used vitreous surgery to treat seven patients (eight eyes) with complicated retinal detachments associated with choroidal colobomas. All eyes had large choroidal colobomas and no evidence of peripheral retinal breaks. Small, atrophic breaks were detected in five of the eyes and were located in the base of the coloboma in four of the five eyes. Adjunctive surgical techniques were necessary and included cyanoacrylate retinopexy in four eyes, silicone oil tamponade in five eyes, and retinectomy in two eyes. Retinal reattachment was ultimately attained in seven of the eight eyes. The number of surgical procedures ranged from one to five, with an average of three. Postoperative visual acuity of the eyes that underwent anatomically successful procedures ranged from 20/100 to light perception. Proliferative vitreoretinopathy was the most frequent cause of redetachment, occurring in six of the eight eyes.

Adult

Altered distribution of basic fibroblast growth factor in diabetic retinopathy.

Basic fibroblast growth factor (FGF) is a potent endothelial cell mitogen that has been proposed to play a role in proliferative diabetic retinopathy and other neovascular processes. Our understanding of the in vivo role of basic FGF in the pathogenesis of these disorders is limited. We studied the immunolocalization of basic FGF in 16 clinical cases of diabetic retinopathy to determine whether the normal retinal distribution of basic FGF changed during the development of diabetic retinopathy and correlated with the onset of retinal neovascularization. By using monoclonal and affinity-purified polyclonal antibodies against basic FGF and heparan sulfate proteoglycan (HSPG), we found that basic FGF colocalized with HSPG to vascular basement membranes. As the basement membranes thickened during the progression of diabetic retinopathy, the intraretinal stores of immunoreactive basic FGF and HSPG expanded. With the development of neovascularization, the colocalization of basic FGF and HSPG changed; HSPG localized to basement membranes, while basic FGF localized intracellularly, with only minimal basement membrane immunoreactivity. Incubations of the neovascular fronds with exogenous basic FGF demonstrated multiple HSPG glycosaminoglycan-binding sites for basic FGF, indicating that basic FGF had not been released from the matrix of neovascular fronds by heparitanase digestion.

Antibodies, Monoclonal

Long-term histologic and electrophysiologic evaluation of the alloy retinal tack.

The retinal tack is a useful adjunctive instrument in the repair of complicated retinal detachments. To examine the tissue response of chronically implanted alloy tacks, we implanted a series of tacks into rabbit eyes. Their effects were observed at 1 and 4 weeks, at 6 months, and at 2.5 years after insertion. Our observations indicate that the histology and electrophysiology of the retina was generally not affected. All tacks were surrounded by connective and/or glial tissue scar and induced firm retinal adherence. The retinal architecture was normal within 1 mm of the scar, indicating that these alloy tacks do not cause tissue damage outside the immediate area of the wound, even when left in place over a period of 2 years.

Alloys

Primary culture of human retinal glia.

Glial cells of the human retina participate in various pathologic processes characterized by cell migration, proliferation, and extracellular matrix production. To study these events in vitro, a procedure was developed to obtain primary cultures of human retinal glial cells. The cultures resulting from the processing of 130 globes contained cells with variable morphology including bipolar and multipolar or stellate cells. Most cells in the primary culture were labeled with antisera to the glial fibrillary acidic protein. The cultures were also examined with antibodies directed against factor VIII-related antigen and muscle-specific actin to determine the presence of endothelial cells and pericytes. A variable contamination of cells staining for the latter was found in these cultures (usually less than 10%). Together, these data indicated that the primary cultures arose principally from glial cells of the human retina but did not precisely identify the cell of origin.

Actins

Blood-retinal barrier breakdown investigated by real-time magnetic resonance imaging after gadolinium-diethylenetriaminepentaacetic acid injection.

Recent magnetic resonance imaging (MRI) studies show that gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) entry into the vitreous space can be used as a qualitative marker of blood-retinal barrier (BRB) disruption. To determine if a more quantitative measurement of BRB breakdown could be obtained, the utility of acquiring real-time, T1-weighted proton images was studied after Gd-DTPA injection. Two days before the MRI experiment, panretinal photocoagulation was done. The mean signal intensity over selected regions-of-interest (ROI) in the vitreous and anterior chamber was followed before and after (0, 10, 20, 30, 45, and 60 min) Gd-DTPA injection (1.0 mmol/kg, intravenously). At every laser power setting used in this study (0, 200, 400, 600, and 800 mW), the change in the mean signal intensity could be approximated by a simple exponential equation. However, the time constants determined for these curves were too imprecise to be useful as correlates between laser power and BRB breakdown. The slope of the line fit to the data in the first 20 min postinjection (ie, an initial-rate analysis) was a more precise correlate between BRB breakdown and laser power. This slope represented the rate of change in mean signal intensity in the ROI as a result of the entry of Gd-DTPA, and it was called the "leakiness" parameter. The leakiness parameter reflected changes in the permeability surface area product of the BRB if the blood flow and the Gd-DTPA arterial concentration immediately after injection were approximately the same between animals.

Animals