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Biomedical subjects

S J Ryan

Publications and source records attributed to S J Ryan.

At least 145 records · Page 8Linked to original sources

Cellular migration, proliferation, and contraction. An in vitro approach to a clinical problem--proliferative vitreoretinopathy.

Presently used animal models of proliferative vitreoretinopathy reflect only cell proliferation and contraction. We used an in vitro model that measured cell migration, proliferation, and contraction. The following four drugs were assayed on this system: daunomycin, taxol, colchicine, and cytochalasin B. Daunomycin was the most effective drug against cell proliferation and cell migration but had no effect on cell contraction; taxol and colchicine affected all three parameters. Cytochalasin B was the least effective drug tested.

Alkaloids↗

An intravitreal cannula system: long-term follow-up study.

An intravitreal cannula for chronic drug delivery was implanted in the eyes of two rabbits and one monkey. The rabbits were followed up for three years after surgery and the monkey was followed up for two and one-half years. Clinical observations did not reveal any adverse effects from the cannula implantation. Patency of the cannula was demonstrated by using sodium fluorescein. Histopathological studies with light and electron microscopy revealed the scar tissue around the cannula to be minimal and localized to the wound site. The optic nerve and the retina and choroid at the posterior pole did not show any abnormalities. These results suggest that this system can be used for repeated or continuous drug delivery to the vitreous over a long period of time in experimental models.

Animals↗

Natural history of penetrating ocular injury with retinal laceration in the monkey.

In one eye each of four cynomolgus monkeys, an 8-mm penetrating injury was made through the equator; there was retinal perforation with vitreous loss. None of the four eyes with this injury developed posterior vitreous detachment or retinal detachment during a follow-up period of 8 months to 1 year. Another group of 26 monkeys had the same injury but also had 0.5 ml autologous whole blood injected into the vitreous at the time of injury. The eyes were examined weekly and enucleated at scheduled intervals from 1 day to 52 weeks post-injury. Posterior vitreous detachment occurred at the earliest at 2 weeks post-injury, and was ultimately present in 91% of the eyes. Vitreous detachment can occur either as a separation at the level of the internal limiting membrane or as a cleavage within the cortical vitreous. Retinal detachment occurred at the earliest at 8 weeks post-injury, and eventually was present in 50% of the eyes. The retinal detachment was tractional; no retinal breaks were detected in any of the eyes.

Animals↗

Effect of the vitreous on retinal wound-healing.

The healing process of experimental retinal wounds in nonvitrectomized and vitrectomized rabbit eyes was compared. Using light, transmission and scanning electron microscopy, a significant difference was observed at the late stages of the healing process. The retinal wounds in the nonvitrectomized eyes healed properly, forming regular and smooth scars, while the scars that developed in the vitrectomized eyes were irregular and hypertrophic. Our observations suggest that the vitreous plays a role in normal healing of retinal wounds.

Animals↗

Aging changes in Bruch's membrane of monkeys: an electron microscopic study.

Bruch's membrane from monkeys of various ages was studied by electron microscopy. In monkeys under 15 years of age, Bruch's membrane rarely contained a small amount of polymorphous material that did not appear to increase with advancing age up to 15 years. However, the polymorphous material did increase over 20 years of age. The accumulation of vesicular, granular, tubular and linear polymorphous material in Bruch's membrane was though to be a result of evagination of a minimal portion of a retinal pigment epithelial (RPE) cell between adjacent basal infoldings, and its subsequent degeneration. The plasma membrane of the evagination seemed to be the primary source of the tubular or linear material, vesicles the main source of vesicular material, and cytosol and basement membranes to be the source of the granular material. The fibrous long-spacing collagen was associated with the basement membrane of the choriocapillaris and RPE cells. The granular deposits between the plasma infoldings and the basement membrane of RPE cells may originate from the basement membrane of the RPE, and could be the initial lesion of basal linear deposits.

Aging↗

Ornithine decarboxylase activity during formation of experimental epiretinal membranes.

This study demonstrates in a rabbit model of epiretinal membrane formation that retinal-associated ODC activity increases during this pathological process. These changes in retinal-associated ODC activity most likely occur in relationship to the proliferative lesion itself, since the retina consists primarily of nonproliferative tissues. Further knowledge of intraocular polyamine metabolism during epiretinal membrane formation which can result in retinal detachment may lead to the development of an effective pharmacological treatment.

Animals↗

Morphological study of epiretinal membrane following posterior penetrating injury in the monkey eye.

Posterior vitreous detachment (PVD) and epiretinal membranes occur in a number of vitreoretinal diseases. We have developed an experimental model in which we can provide the morphologic correlation of these dynamic processes. The method provides the opportunity to study epiretinal membrane formation with the scanning electron microscope (SEM); with SEM, some epiretinal membranes that could not be readily detected either clinically or by routine light microscopy can now be identified and studied in detail. We performed an experimental posterior penetrating injury with injection of autologous whole blood or blood and lens material into the vitreous. Five eyes with posterior vitreous detachment but no retinal detachment were selected for SEM. A reduction in the cortical vitreous filaments and the presence of epiretinal membranes was apparent with SEM. In most areas the epiretinal membranes were separated from the internal limiting membrane by a narrow cleft; however, limited attachment sites between the epiretinal membranes and retina were observed in areas overlying retinal blood vessels. In two eyes we observed microscopic retinal folds beneath the membranes, demonstrating a possible morphologic correlation between epiretinal cellular contraction and traction on the retina.

Animals↗

Pathogenesis of drusen in the primate.

Two monkey eyes that showed clinical evidence of drusen were studied by light and electron microscopy. The drusen-like spots had several different morphological patterns: the appearance of typical drusen, budding retinal pigment epithelial (RPE) cells, and vacuolation of retinal pigment epithelial cells. Several stages of budding were seen. In some lesions, part of the RPE cell protruded into the sub-RPE space. The upper portion of the budding cell was connected to the cytoplasm of the parent RPE cell and was surrounded by basement membrane of the RPE cell. These budding cells had plasma membranes, cytoplasm that contained organelles, and a nucleus. Disconnected buds, separate from the parent RPE cell, were also seen; these showed degeneration. Finally, an accumulation of vesicular, granular, tubular and linear material was found in the nodular space beneath the RPE cell. It is suggested that this budding of RPE cells is the initial event in drusen-formation.

Animals↗

Newly-formed subretinal vessels. Fine structure and fluorescein leakage.

The ultrastructure of experimentally induced newly formed subretinal vessels was correlated with the amount of fluorescein leakage demonstrated by the neovascular membranes during angiography. The membranes that demonstrated leakage contained subretinal vessels with a fenestrated endothelial wall and intermediate interendothelial cell junctions. As these subretinal plexi matured, they stopped demonstrating leakage. This involution process was accompanied by the formation of focal interendothelial tight junctions; however, loss of fenestrations was not observed. The membranes that never demonstrated fluorescein leakage also contained fenestrated subretinal vessels at both early and late stages of development; and their interendothelial junctions showed similar maturation from open to focal tight junctions. Thus all subretinal vessels had "leaky" morphology strongly resembling that of the normal choriocapillaris, whether they demonstrated fluorescein leakage or not. The authors conclude that newly formed subretinal vessels retain the characteristics of the choriocapillaris from which they are believed to proliferate; they have the potential to leak fluorescein at all stages of their development. The absence of fluorescein leakage during angiography cannot always be correlated with the absence of "leaky" morphology.

Animals↗

The role of retinal pigment epithelium in the involution of subretinal neovascularization.

The extravascular milieu around laser-induced experimental subretinal neovascularization (SRN) was studied during the evolution of the neovascular membrane from its early leaky stage to its late involuted stage. When the first signs of visible leakage appeared on angiography, newly formed vessels were spread in the subretinal space around the break in Bruch's membrane, fluid was accumulating in the subretinal space, and retinal pigment epithelial (RPE) cells were proliferating in a papillary pattern around the newly formed vessels; the RPE proliferation began with the undamaged cells at the edges of the laser injury. With further maturation, the RPE continued to envelope the subretinal vessels. This RPE proliferation was associated with the disappearance of fluid between the enveloped vessels and the sensory retina, and the gradual cessation of fluorescein leakage during angiography. At the end of the involution process, when the neovascular membrane no longer demonstrated any leakage, the subretinal vessels were found to be tightly enveloped by RPE cells, and no fluid separated them from the sensory retina. The authors' results suggest that involution of the neovascular membrane with maturation, as demonstrated by the cessation of visible fluorescein leakage, is the result of RPE proliferation that tightly envelopes the newly formed vessels and probably resorbs the previously accumulated subretinal fluid, as well as preventing its further accumulation in the subretinal space.

Animals↗

Diffuse drusen and associated complications.

An eye of a patient with an unusual form of diffuse drusen was studied by light and electron microscopy. Examination disclosed marked diffuse and nodular thickening of the inner portion of Bruch's membrane by vesicular and curvilinear membranous profiles and basement membrane-like material that was apparently derived from the retinal pigment epithelium. Deposition of this abnormal material suggests a diffuse abnormality of the retinal pigment epithelium and predisposes to serous detachment of the retinal pigment epithelium, choroidal neovascularization, hemorrhagic detachment of the retinal pigment epithelium, and disciform scarring. The features of this case are similar to previously reported cases of diffuse drusen, but differ in the early age of onset, intensity of changes, and, in part, by the nature of the abnormal material observed.

Basement Membrane↗

The pathophysiology of proliferative vitreoretinopathy in its management.

Cellular proliferation following retinal reattachment surgery frequently results in contraction and subsequent recurrent detachment of the retina, negating an initial successful reattachment. This process has been called by a variety of names, such as massive vitreous retraction, massive preretinal retraction, and, more recently, proliferative vitreoretinopathy. Although a good start has been made by the Retina Society to classify the various types of proliferative vitreoretinopathy, some modifications in the classification are required. The fundamental problem in the treatment of proliferative vitreoretinopathy is a lack of knowledge regarding the factors that stimulate the proliferation of cells. The vitreoretinal surgeon should recognize in the life cycle of this process that stage which an eye with retinal detachment has reached. If there is no active cellular proliferation, then a scleral buckle will usually suffice. If there is traction from epiretinal membranes which cannot be relieved by a buckle, then vitrectomy and adjunct procedures are necessary. If there is active cellular proliferation and epiretinal membranes, then the arguments related to proper timing of vitrectomy must be considered. In cases where the retinal holes can be identified and closed, scleral buckling may be performed with subsequent delayed vitrectomy. In most cases, in my experience, a combination of revision of the scleral buckle is required at the time of vitrectomy and membrane segmentation for proliferative vitreoretinopathy. Until such time as drugs are available to inhibit cellular proliferation or until our basic understanding of the cell biology of this process allows other means of pharmacologic intervention, mechanical approaches will remain necessary for the treatment of the most advanced cases.

Cryosurgery↗

In vitro measurement of contractile force of transvitreal membranes formed after penetrating ocular injury.

We adapted a preloaded isometric microstrain gauge force transducer system to measure in vitro the contractile strength of intravitreal fibrocellular membranes formed after reproducible posterior penetrating injury to the eye. We demonstrated that these intravitreal membranes reversibly contracted to serotonin, norepinephrine bitartrate, angiotensin II, prostaglandin F1 alpha, bradykinin, and vasopressin as well as when placed in a depolarizing solution or if electrically stimulated. The membranes could be subsequently relaxed with papaverine hydrochloride, cytochalasin B, and diltiazem hydrochloride. We further demonstrated adrenergic receptor sites on these membranes. We were unable, however, to demonstrate any response to histamine or acetylcholine. Based on these findings, we postulate that the intravitreal membranes formed after perforating ocular injuries bear a functional similarity to smooth muscle and the contractile tissue formed after injury elsewhere. These membranes are of basic importance in the pathogenesis of traction retinal detachment.

Angiotensin II↗

Severe ocular injuries from orthodontic headgear.

Dislocation of extraoral orthodontic tractional devices (headgear) resulted in penetrating ocular injuries in three eyes of two patients. An endophthalmitis caused by mixed flora developed in each injured eye. Despite medical and surgical therapy, only one eye retained useful vision two years following injury. All wearers of headgear and their families should be educated in the proper use of these devices and about the potential for severe facial injuries. Penetrating ocular injuries initially may be relatively asymptomatic. Thus, even persons with seemingly minor injuries from such devices should seek immediate and thorough ophthalmic evaluation. In eyes with penetrating injuries, culture of intraocular fluids should be performed at the time of initial repair. Because the penetrating device is heavily contaminated with oral flora, broad-spectrum antibiotics should be administered by intravenous, subconjunctival, and intravitreal injection. Such injuries, although rare, may have a grave prognosis.

Adolescent↗

Effects of intravitreal administration of steroids on experimental subretinal neovascularization in the subhuman primate.

To elucidate the role of inflammation in the occurrence of experimental subretinal neovascularization caused by high-intensity laser photocoagulation, we investigated the effects of vitreal infusion of steroids on laser lesions in a primate model. Dexamethasone, with or without triamcinolone, was infused continuously for two weeks through an indwelling cannula system. The animals were followed up clinically for up to eight weeks. The frequency of subretinal neovascularization in the steroid-treated animals was significantly lower than that in a control group of untreated animals. Although steroids have multiple effects, these results suggest that the inflammatory response, possibly macrophage infiltration, may plan an important role in the occurrence of subretinal neovascularization in our experimental model.

Animals↗