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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.

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.

A controlled trial of pars plana vitrectomy for posterior penetrating eye injury was done in a group of rhesus monkeys to compare the results of limited (core) and complete vitrectomies performed one day and two weeks after injury. Although core vitrectomy was technically easier and led to fewer operative complications, the frequency of traction retinal detachment was significantly higher than after a complete vitrectomy. There was no significant difference between eyes operated on one day or two weeks after injury.

The principles and guidelines in the management of penetrating ocular injury are detailed. In the absence of definitive clinical trial or an experimental model, the rationale for pars plana vitrectomy has been presented. In addition, our recommendations as to the appropriate role and timing of pars plana vitrectomy are included.

Perfluoropropane gas was injected into the vitreous body of a primate eye. Clinical and morphologic studies revealed that the gas bubble created a large cavity within the vitreous. The cavity that subsequently filled with viscous liquid was completely enveloped by vitreous gel, thus simulating the clinical condition known as vitreous syneresis. The shell of residual vitreous, which was much thicker inferiorly and behind the lens than superiorly, seemed to be an intact and continuous layer. In spite of the extensive syneresis, posterior vitreous detachment failed to develop. Our findings suggest that a vitreous cavity, voluminous as it may be, is not sufficient to cause posterior vitreous detachment in the primate eye.

Visual improvement was achieved in 62% of 100 consecutive patients with ocular trauma treated by pars plana vitrectomy. Anterior segment injuries had a better prognosis than posterior segment injuries, and retinal detachment was a poor prognostic sign. Patients undergoing vitrectomy during the two weeks after injury had a better visual prognosis than those who had delayed vitrectomy. Pars plana vitrectomy has increased the recovery rate in traumatized eyes which previously were deemed inoperable and frequently were enucleated. Most such eyes have intraocular fibrocellular proliferations, resulting in traction retinal detachments, cyclitic membranes, and phthisis, as documented in clinicopathological and experimentally produced specimens of penetrating ocular trauma. Vitrectomy can interrupt this sequence, if performed one to 14 days after injury, by removing the vitreous scaffold onto which proliferation occurs, together with the elements of hemorrhage, damaged lens, vitreous, and foreign material which may incite proliferation. We believe four to ten days after injury to be the optimal time for vitrectomy to avoid the hazards of immediate intervention, while removing damaged tissue before serious sequenlae occur.

The clinical appearance, fine structure, and permeability to horseradish peroxidase and fluorescein of subretinal neovascularization (SRN) in monkeys was correlated at various stages of vessel development: early (active leaking), intermediate (slightly leaking), and regressive (nonleaking). The degree of SRN permeability correlated well with the presence of endothelial cell fenestrations. The substantial changes in the fine structure and permeability of SRN during maturation can account for the different clinical manifestations. It is thus apparent that the time of morphologic correlation must be considered when studying a dynamic evolving process, such as SRN.

A new experimental model of subretinal cellular proliferation, based on injection of autologous vitreous into the subretinal space of rabbits, was studied by light and electron microscopy. As early as five days after injection, proliferation of retinal pigment epithelial (RPE) and retinal glial cells was observed in the subretinal space. These morphologically distinct proliferating cells were sometimes joined by junctional complexes. Morphologically, the proliferating RPE cells resembled either RPE cells or fibroblasts. Some proliferating RPE cells also retained their epithelial characteristics (ie, basement membranes and cell junctions), while others were partially dedifferentiated and showed some embryonic features. New formation of melanin could be identified within the proliferated RPE cells, which could account, in part, for the hyperpigmentation at the site of the bleb caused by the injection of vitreous. The results demonstrated that injection of autologous vitreous into the subretinal space can lead to subretinal proliferation of retinal glial and RPE cells in the rabbit.

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.

Transplantation of from 10,000 to 750,000 autologous and homologous dermal fibroblasts into the vitreous cavity of rabbit eyes resulted in identical clinical findings leading to massive periretinal proliferation. A dose-response relationship between the number of cells injected and the extent of retinal traction that developed was established. The second phase of the experiment evaluated the effects of formalin and cobalt irradiation on the fibroblasts' ability to cause traction retinal detachment. Cell proliferation or the attainment of a critical mass of living cells was necessary for the development of traction retinal detachment.

Traumatic posterior vitreous detachment was studied in a monkey model of posterior penetrating eye injury with retinal laceration and intravitreal blood. Posterior vitreous detachment can occur as a separation at the level of the internal limiting membrane, or as a cleavage within the vitreous. The foot processes of Mueller cells were found to be altered in eyes with detached vitreous. Epiretinal membranes were seen to proliferate through cracks in the internal limiting membrane. The internal limiting membrane beneath the epiretinal membrane appeared to be wrinkled, suggesting a contractile property of the epiretinal membrane. The plane of separation in posterior vitreous detachment may be of fundamental importance in the formation of epiretinal membranes and subsequent development of retinal detachment.

We studied the ultrastructural characteristics of an experimental model of traction retinal detachment secondary to a penetrating eye injury in the rhesus monkey. Cells with the characteristics of myofibroblasts were present in the intravitreal fibrous tissue and in epiretinal membranes. These cells were probably derived from many sources, and were capable of contraction through the mechanism of intracytoplasmic contractile proteins such as actin or myosin. The morphologic observations supported our hypothesis that traction retinal detachment is a cell-mediated event analogous to the processes of wound healing and wound contraction. The force of contraction is mediated by cell-to-cell and cell-to-vitreous connections and by glial bridges that connect epiretinal membranes to the retina. These ultrastructural studies, which provide insight into the pathogenesis of traction retinal detachment in the experimental animal model, may well have significant clinical relevance.

A fibroblast induced model of retinal membrane has been developed in the vitrectomized rabbit eye. Localization of the membrane on the retinal surface requires a two stage procedure. An initial lensectomy and vitrectomy results in partial posterior vitreous detachment; the vitreous remains attached to the vascular retina (medullary rays) and vitreous base. At a subsequent procedure the detached posterior hyaloid face is excised; a fluid/SF6-air exchange is performed and fibroblasts are injected. Despite the use of only 25,000 cells, retinal membrane and subsequent traction retinal detachment develop. In contrast to cell injection in the nonvitrectomized eye, in which vitreous membranes predominate, this model stresses epiretinal membrane and surface retinal traction.

A technique has been developed which produces an experimental posterior penetrating eye injury that reproducibly results in traction retinal detachment in rabbit eyes. The standard injury is an incision through the pars plana with vitreous prolapse and incarceration; the wound is then carefully closed with microsurgical techniques. It appears that blood in the vitreous is an essential factor in the development of vitreous traction and of traction retinal detachment. The model, which has been successfully transferred to Rhesus monkey eyes, is considered useful for further histological, electromicroscopical, electrophysiological, and ultrasound studies of posterior penetrating injuries of the eye. Our immediate goal is to assess in a controlled experiment whether pars plana vitrectomy can interrupt the sequence of events leading to traction retinal detachment after a posterior penetrating injury.

In previous studies the authors have shown that daunomycin, an anthracycline antibiotic, when injected into the vitreous effectively controls experimental proliferative vitreoretinopathy. Here we show that by administering daunomycin intravitreally it is possible to achieve in vivo concentrations that prevent fibroblast proliferation in vitro. The authors have also determined that the half-life of daunomycin in the vitreous is 131 min, indicating that a critical concentration is maintained in the eye for longer than 4 hr after a single injection. Using 3H-daunomycin, the authors have found that the drug is eliminated across the retina; no significant binding of the drug to vitreous components occurs. These studies demonstrate that it is possible to define the kinetics of drugs injected into the vitreous; and a knowledge of the distribution of any drug in ocular tissues is necessary to effectively determine whether such drug is of therapeutic value.

The retinal toxicity of daunomycin, a drug that effectively suppresses experimental proliferative vitreoretinopathy (PVR), was studied in the rabbit by clinical examination, electroretinography (ERG), light microscopy, and electron microscopy. Although no toxicity was observed at the therapeutically effective dose of 10 nmol per eye, the safety margin is too small to recommend this drug for therapy of proliferative vitreoretinopathy in man.

A controlled trial of pars plana vitrectomy for posterior penetrating eye injury was done in rhesus monkeys. After standard injury, each eye was allocated randomly into a treatment or control group. Treatment groups (ten eyes each) had vitrectomy at 1, 14, or 70 days after injury. The control group had 15 eyes. The same techniques were employed as in human eyes. Surgical objectives were lensectomy, then complete posterior vitrectomy and excision of the anterior vitreous to within 1 or 2 mm of the surface of the peripheral retina and pars plana. Results from this controlled trial provide strong support for the effectiveness of vitrectomy techniques in managing selected posterior penetrating injuries in human eyes and in preventing the complication of traction retinal detachment.

A method was established for chronic drug delivery into the vitreous of the rabbit eye. A cannula was inserted into the eye through the pars plana. A silicone plate controlled the intraocular location of the tip of the cannula; this plate also served as an anchor plate to the sclera. The distal end of the cannula was attached via a larger diameter silicone tubing to an implanted osmotic mini-pump. Cannulas remained patent and there was almost no evidence of ocular trauma after one year follow-up. This method thus has a potential use for experimental studies involving chronic application of drugs.

The effect of intraocular liquid silicone on the electroretinogram (ERG) and on retinal morphology was studied in rabbits. After vitrectomy, liquid silicone (1000 centistokes) or balanced salt solution (BSS) was injected into the eyes. The intraocular silicone was well tolerated clinically in all eyes that were followed over a period of 3 days to 6 months. ERG responses were equivalent in operated control and silicone-injected eyes. Light and electron microscopy showed slight but comparable changes in both operated control and silicone-injected eyes that were consistent with either fixation artifact and/or surgical trauma. The results suggest that exposure to silicone for up to 6 months does not have a toxic effect on the rabbit retina.

The distribution of fibronectin and laminin in diabetic human eyes was determined by indirect immunofluorescent techniques. The intense fluorescence suggests increased amounts of fibronectin and laminin in the diabetic internal limiting membrane (ILM). A double laminated pattern of fluorescence for both glycoproteins suggests structural abnormalities of the ILM of the posterior retina. Preretinal and subretinal proliferative tissues fluoresced strongly and diffusely with antifibronectin. This study indicates that in diabetic patients, the ILM, especially in the posterior retina, is biochemically and morphologically abnormal.

We developed an experimental model for a posterior penetrating eye injury that resulted in traction retinal detachment in 21 rhesus monkey eyes. The standard injury was an incision through the pars plana with vitreous prolapse and incarceration; the wound was then carefully closed with microsurgical techniques. At one to two weeks after injury, detachment of the posterior vitreous occurred and detachment of the retina occurred between seven and 11 weeks. The development of retinal detachment was related to traction on the peripheral retina over the vitreous base; and to the contraction of epiretinal membranes on the peripheral and equatorial retina. Our study supports clinical observations on the importance of blood in the vitreous in the development of vitreous traction and traction retinal detachment after a posterior penetrating injury.

A 22-year-old man was seen with the ocular histoplasmosis syndrome. This case demonstrates that spontaneous or "de novo" neovascularization without prior pigmentary changes can occasionally, although rarely, give rise to the disciform macular disease process and the potential for loss of central vision. The lesion initially responded favorably to treatment with heavy argon laser photocoagulation in the parafoveal area, including the papillomacular area, but subsequent areas of neovascularization proved intractable to laser therapy.

Neovascularization and proliferation of the retinal pigment epithelium (RPE) was induced in the rabbit by subretinal injection of vitreous without rupture of Bruch's membrane. New vessels developed between the layer of RPE and photoreceptor outer segments, but were enveloped in proliferating RPE. For this reason they were occult; no fluorescein leakage was visible by angiography. The vessels were identified only by histologic examinations. Endothelial cell budding was the initial stage of vessel development, first seen two weeks after injection. The new vessels grew from the choriocapillaris, penetrated Bruch's membrane, and spread into the subretinal space, despite the absence of subretinal fluid. Fenestrations with diaphragms were found in the endothelial walls during the earliest stages of vessel formation, and were also present in the fully matured vessels. Intermediate junctional complexes were frequently observed among the endothelial cells. During maturation of these plexi, junctions changed from open to putative tight junctions. The mature vessels were ultimately completely enveloped by collagen and RPE cells. Our results show that all new vessels in this animal model have the morphologic characteristics of choriocapillaris. We assume that they leak fluorescein, as does the choriocapillaris, but that the dye has no opportunity to pool in the subretinal space and thus cannot be seen during angiography.

Mechanical and enzymatic disruption of Bruch's membrane and induction of subretinal neovascularization in an experimental primate model have produced limited success. The methods and results are reported here to identify some problems encountered in methodology and to detail the results of this approach to subretinal neovascularization.

The vitreous is felt to play a significant role in the development of advanced proliferative sickle retinopathy. This is particularly true in Stages 3 to 5 of the Goldberg classification. A comparison with the classification of proliferative diabetic retinopathy by Davis is presented. The role of vitrectomy in this disorder has been considered.

Condensation and contraction of the vitreous have been implicated in the development of vitreoretinal traction and traction retinal detachment after penetrating ocular injury. In this study, using the inorganic dye ruthenium-red, we studied ultrastructural changes in vitreous in the rabbit eye after standard penetrating injury and intravitreal blood injection. In normal rabbit vitreous the collagen fibrils have a regular arrangement. In contrast, after a penetrating injury the collagen fibrils appear focally condensed. While it appears unlikely that such a network could alone produce tractional or directional forces, these alterations along the collagen fibrils could provide a scaffold along which contractile cells migrate into the vitreous.

Macrophages, which migrate into the vitreous in conditions such as vitreous hemorrhage and penetrating ocular injury, may contribute to the development of intravitreous cellular proliferation and posterior vitreous separation. To investigate this possibility, activated macrophages were harvested from the peritoneal cavity and injected into the vitreous of rabbits. As early as 8 days after macrophage injection, posterior vitreous separation and glial epiretinal membrane formation began to occur. Two weeks after injection, vitreous strands that approached the optic disc and medullary rays were evident; fibroblasts proliferated over the disc or rays and induced retinal detachment. These findings support the hypothesis that macrophages in the vitreous may, in part, mediate cellular proliferation and posterior vitreous separation.

Thirty-four severely injured eyes were operated with pars plana vitrectomy. The nine cases with involvement exclusively of the anterior segment alone were operated with success in all cases. However, the injuries of the posterior segment still reflect significant problems in that only 50 percent obtained successful visual results. This reflects, in great part, the degree of severity of the initial damage. The theoretical rationale for pars plana vitrectomy in penetrating ocular trauma is discussed. Because of the many variables from patient to patient and injury to injury, conflicting clinical impressions as to appropriate management prevail. In the abscence of a definitive clinical trial or suitable experimental model, our guidelines for the role and proper timing of pars plana vitrectomy for penetrating ocular trauma are presented.

In order to compare the known morphological changes which occur during the postnatal development of the salivary glands in the rat with alterations in membrane function, we measured adenylate cyclase activity and its responses to sodium fluoride (NaF), norepinephrine, and isoproterenol in salivary gland membranes at various times after birth. In the parotid gland, basal enzyme activity did not change significantly during postnatal life, but fluoride-stimulated activity rose on day 15; A similar marked rise in activity stimulated by norepinephrine (0.02 mM) and isoproterenol (0.03 mM) was noted simultaneously. In the submandibular gland, basal adenylate cyclase activity was higher just after birth than at 25 days of life or in maturity. Fluoride-stimulated activity was 7 times higher than basal activity on day 1, greater than 10 times higher on day 25, and 30 times greater in the adult. The gland was as responsive to norepinephrine and isoproterenol on day 5 as it was on day 25 or in the mature animal, showing a two- to threefold increase over the basal enzyme value at each time point studied. Residual phosphodiesterase activity in the membranes was always negligible. The data demonstrate a time-dependent developmental change in the responsiveness of the parotid gland to norepinephrine and isoproterenol, which corresponds to the time when morphological maturation normally occurs. By contrast, in the submandibular gland, membrane-bound adenylate cyclase is fully developed at the time of birth.

Macrophages are fully differentiated cells that do not synthesize an extracellular matrix and do not contract; they do, however, produce substances that modify the behavior and functions of other cells, particularly those involved in the inflammatory and immune responses. Since macrophages are a ubiquitous component of periretinal membranes, we sought to determine whether they modulate proliferation and/or migration of retinal pigment epithelial (RPE) cells, functions that may be essential for the development of proliferative vitreoretinopathy (PVR). Using an in vitro assay, we found that macrophage supernatant contains factors that stimulate proliferation and migration of cultured human RPE cells. Since interleukin-1 (IL-1) is a product of activated macrophages that modulates a number of cellular functions, we also examined its effect on RPE proliferation and migration. We found that IL-1 increased migration but did not affect proliferation, and thus could not duplicate the effect of macrophage supernatant. Injection of activated macrophages into the vitreous of rabbits which had a retinal hole stimulated RPE cell proliferation in the area of the retinal hole, where the RPE cells were exposed. These findings suggest the ability of macrophages to modulate functions of RPE cells that are thought to be critical for the development of PVR. Macrophages may thus be an important part of the vitreous environment that favors the development of PVR.

The distribution of fibronectin in the chorioretinal interface of the monkey eye was studied by indirect immunofluorescent and immunoelectron microscopic techniques. Immunofluorescent staining revealed fibronectin in Bruch's membrane and the choriocapillaris. Immunoelectron microscopic techniques revealed fibronectin associated with basement membranes, collagen fibers and elastic fibers in Bruch's membrane; the stromal side of the basement membrane of the choriocapillaris also showed staining. This study thus demonstrates that fibronectin is an integral component of Bruch's membrane in the monkey eye.

The topographic distribution of fibronectin and laminin in young and old human eyes was determined by indirect immunofluorescent techniques. These two glycoproteins may play a role in the attachment of the vitreous to the internal limiting membrane (ILM) and the internal limiting membrane to the Mueller cell processes. A double-laminated pattern of fluorescence for both glycoproteins was frequently found at the ILM of the posterior retina of aged eyes. This pattern of fluorescence, which was rarely seen in young eyes, may represent senescent changes in the ILM which could predispose the eye to posterior vitreous detachment.

It was recently shown that the injection of autologous vitreous beneath the retina of rabbits leads to retinal degeneration, subretinal cellular proliferation and neovascularization. The current study, using electron microscopy, was designed to determine the cellular processes involved in the breakdown of Bruch's membrane in this model. Bruch's membrane was not mechanically damaged by the injection and appeared intact for the first 1 to 2 days after injection. Subsequently, numerous breaks in Bruch's membrane were found associated with invasion of macrophages and fibroblasts; in addition, budding and penetration of retinal pigment epithelial (RPE) and choroidal endothelial cells into Bruch's membrane were noted. Although it was not proven that these cells, per se, were responsible for the breaks, that these cells actively penetrate Bruch's membrane is a reasonable hypothesis.

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.

Retinal pigment epithelial (RPE) cell migration and proliferation are believed to play a role in the pathogenesis of proliferative vitreoretinopathy (PVR). Since PVR develops in situations where vitreous contacts the RPE, we sought to determine whether human vitreous contains factors that stimulate proliferation and migration of RPE cells. We found that postmortem human vitreous stimulates migration but not proliferation of human RPE cells under serum-free conditions in vitro. Stimulation of proliferation of RPE cells and fibroblasts was observed, however, following admixture of albumin with the vitreous. These findings suggest that vitreous contributes modulators that stimulate some functions of RPE cells that are believed to play a role in the pathogenesis of PVR.

Light and electron microscopy of drusen formation in the human eye showed yellow-white spots in the fundus with two morphologic patterns: that of typical drusen and a nodular accumulation of cellular components beneath the retinal pigment epithelial cells. By electron microscopy, the progression of drusen formation could be classified into four stages. Stage I showed budding or evagination of retinal pigment epithelial cells into the subpigment epithelial space. This evaginated portion was connected to the retinal pigment epithelial cell cytoplasm and was surrounded by its basement membrane. In Stage II the evaginated portion of the cell was completely separate from the cytoplasm of its parent retinal pigment epithelial cell. In Stage III, the evaginated portion showed degeneration and disintegration. Finally, in Stage IV, an accumulation of vesicular, granular, tubular, and linear material was seen free within the nodular space beneath the retinal pigment epithelial cell.

There are very few eyes with the ocular histoplasmosis syndrome that have been studied as such by the ophthalmic pathologist. Hoefnagels and Pijpers [6] were the first to demonstrate H. capsulatum in the human eye. However, this was a case of endophthalmitis and not the clinically observe syndrome. Klintworth et. al. [7] demonstrated the organism histologically in granulomatous choroiditis occurring in dissemiated histoplasmosis. The hot was compromised immunologically, and this again is somewhat different from the typical clinical situation. The histopathological material available for study was derived from the eyes of patients enucleated after the diagnosis of malanoma at the AFIP, nd from autopsy material from the Wilmer Institute. These five cases have a number of findings in common. The atrophic scars and punched-out sponts in the periphery and elsewhere correlate with an absence of the pigment epithelium. The degree of inflammation, usually lymphocyte infiltration, can be variable...

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.

In proliferative vitreoretinopathy (PVR), retinal pigment epithelial (RPE) cells migrate into the vitreous, where they may acquire a fibroblast-like morphology. Such cells may eventually form contractile periretinal membranes, resulting in traction retinal detachment. Among the environmental influences that could cause this change in RPE phenotype, exposure to vitreous and to macrophages is most obvious, as macrophages are invariably found in epiretinal membranes and precede membrane formation in experimental traction retinal detachment. We initiated studies to define modulation of cultured RPE cell morphology by exposure to vitreous or to macrophage-conditioned media. Vitreous, serum, and albumin alone had no effect on the epithelial appearance of RPE cells in vitro. However, macrophage-conditioned media and vitreous-serum or vitreous-albumin mixtures induced a reversible fibroblast-like appearance in these cells. These findings show that macrophages produce a morphoplastic substance for RPE cells, and suggest that vitreous also contains a factor(s) that affects RPE cell shape, and that requires mediation by serum components.

The actions of adrenaline, noradrenaline and isoprenaline on the resistance to outflow of aqueous humour from the rabbit eye are described. In some experiments, correlations have been made with pupil diameter. Intravitreous injections of adrenaline, noradrenaline and large doses of isoprenaline decreased the resistance to outflow of fluid from the eye and dilated the pupil. Intravitreous injection of phentolamine was without effect on the intraocular pressure and resistance to outflow of aqueous humour, although such injections resulted in miosis. The actions of adrenaline, noradrenaline and large doses of isoprenaline on the outflow resistance were antagonized by phentolamine. Postganglionic sympathetic denervation did not affect the aqueous humour dynamics when the eyes where examined 2 weeks later, but all the denervated eyes exhibited miosis at this time. Much smaller doses of noradrenaline were required to lower the intraocular pressure and decrease the resistance to outflow of aqueous humour in the denervated eyes; in addition, the dose/response curve for the effect of noradrenaline on the outflow resistance was shifted to the left in these experiments. These results support the view that adrenaline alpha-receptors are associated with the resistance to outflow of aqueous humour from the rabbit eye.