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P Hiscott

Publications and source records attributed to P Hiscott.

At least 55 records · Page 3Linked to original sources

Recognition of vitreoschisis in proliferative diabetic retinopathy. A useful landmark in vitrectomy for diabetic traction retinal detachment.

INTRODUCTION: In the late stages of proliferative diabetic retinopathy (PDR) the vascularized posterior cortical gel (PCG) contracts leading to a partial posterior hyaloidal separation, hemorrhage, and traction retinal detachment (TRD). "Additional epiretinal membranes" have been described previously. These are thin, usually transparent epiretinal membranes which extend anteriorly from the point of attachment of the elevated posterior cortical gel to the edge of the TRD. The origin and frequency of the occurrence as well as the clinical significance of such additional epiretinal membranes are the subjects of controversy. PURPOSE: To quantitate the authors' clinical impression that additional epiretinal membranes are common in advanced PDR, to characterize them immunohistochemically, and to demonstrate the rationale for the authors' surgical approach. METHODS: Intraoperative observations for all patients undergoing diabetic vitrectomy and delamination over the last 2 years were reviewed retrospectively. The presence of additional epiretinal membrane was searched for in the initial stages of vitrectomy. When identified, their apparent continuity with the elevated portion of the PCG was confirmed. Surgical specimens were obtained from nine patients for immunohistochemical study. RESULTS: Additional epiretinal membranes were observes in 145 (81%) of 179 consecutive eyes with PDR that underwent surgery for macular TRD. Immunohistochemical staining with type II collagen antibody was positive in all specimens, suggesting that these membranes were of vitreous origin. CONCLUSIONS: It is likely that the additional epiretinal membranes represent the posterior leaf of a split PCG, the anterior leaf being the elevated portion of the PCG. The two leaves remain fused in the main, fibrovascular portion of the epiretinal membrane. These findings help explain the clinical experience that once the posterior leaf of the PCG is identified and elevated, it provides an accurate point of entry into the surgical plane facilitating delamination of the fused (vascularized) portion of the PCG from the detached retina.

Aged↗

Non-vascular vitreoretinopathy: the cells and the cellular basis of contraction.

BACKGROUND: We consider epiretinal membrane in terms of the two repair processes of gliosis and fibrosis and look at the cellular basis of contraction. METHODS: Pathological material removed at surgery was examined by a range of morphological procedures. Cultures of fibroblasts, retinal pigment epithelium cells and retinal glia were subjected to bioassays which relate to behavioural activities in scar formation. RESULTS AND CONCLUSIONS: Our findings highlight the importance of activities such as migration and adhesion in the formation of epiretinal membranes, and also show that these activities are central to our understanding of contraction.

Animals↗

'En bloc' dissection of epimacular membranes using aspiration delamination.

'En bloc' dissection is a technique in which epiretinal membranes (ERM) are separated from the retina as a single lamina with a 20-gauge blunt flute needle. We used this technique to remove epimacular membranes of various aetiologies in a consecutive series of 25 eyes, with a minimum follow-up of 5 months (mean 10.4 months). Small residual epicentres of ERM away from the fovea remained in 7 (29.1%) eyes only; 3 were inside and 4 outside the temporal vascular arcades. Postoperatively 64% (16/25) of patients achieved a final visual acuity of 6/12 or better and 76% (19/25) achieved a final visual acuity of 6/18 or better. Progressive lens opacities were the most important postoperative complication in phakic eyes that significantly affected the visual results. This technique successfully removed epimacular membranes over a wide area, without the need to find a starting edge or the use of sharp instruments near the retina. Diaphanous ERMs with ill-defined borders and tenaciously adherent membranes could be removed with minimal trauma to the underlying retina. Histopathological and immunohistochemical examination of 10 ERMs demonstrated the absence of internal limiting lamina in 6 (60%).

Adolescent↗

Morphological response to UV-B irradiation after excimer-laser photorefractive keratectomy.

The purpose of this study was to evaluate the morphological effects of UV-B exposure on the outcome of photorefractive keratectomy (PRK). A total of 42 pigmented rabbits were used in the study. In all, 1 eye of 12 rabbits received a 193-nm and 45-micron-deep (-5.0-D) excimer-laser PRK, 1 eye of 12 rabbits received a 135-micron-deep (-15.0-D) excimer-laser PRK and 1 eye of 12 rabbits received a 270-micron-deep (-30.0-D) excimer-laser PRK. At 21 days after PRK, six of the laser-treated eyes from each group were exposed to 100 mJ/cm2 UV-B (280-320 nm) light by placement of the rabbits in a standard clinically used "dermatological chamber" for 7 min. One eye of six rabbits received only UV-B light, serving as a control. The other six rabbits from the PRK groups received no further treatment. Subepithelial "haze" was evaluated before and after UV irradiation. Corneal morphology was assessed at 4, 8 and 12 weeks after UV-B exposure by light microscope and transmission electron microscope techniques (TEM). Eyes exposed to 100 mJ/cm2 UV-B light exhibited only keratitis for 2 days but showed no haze and were histologically normal at all time points. The PRK-treated, UV-B-irradiated rabbit eyes exhibited a significant increase in stromal haze as compared with the eyes receiving PRK alone; this phenomenon correlated with the depth of photoablation. Histologically, the main difference observed between the UV-B-irradiated and nonirradiated post-PRK eyes was the presence of anterior stromal extracellular vacuolization in the UV-B-exposed eyes. The vacuolated foci were confined to the PRK treatment area, contained increased numbers of keratocytes and showed a disorganization of normal collagen lamellae. TEM revealed activated keratocytes containing abundant rough endoplasmic reticulum, prominent Golgi zones and extracellular vacuoles filled with amorphous material. The haze and morphological changes showed a tendency towards incomplete resolution over a period of 12 weeks. UV-B exposure during post-PRK stromal healing exacerbates and prolongs clinical symptoms and the stromal healing response in rabbits, which is manifested biomicroscopically by augmentation of subepithelial haze. The findings suggest that excessive ocular UV-B exposure should be avoided during the period of post-PRK stromal repair (at least 3 months) and that UV-B light may modulate the response of tissues to 193-nm excimer and, perhaps, other laser energy in general.

Animals↗

Insulin-like growth factor I (IGF-I) receptor/binding protein in human diabetic epiretinal membranes.

Insulin-like growth factor I (IGF-I) is thought to play a role in the development of proliferative diabetic retinopathy. Proliferative diabetic retinopathy is characterised by the formation of fibrovascular epiretinal membranes, and IGF-I may initiate and/or potentiate this epiretinal proliferation. To evaluate further the part played by IGF-I in the development of epiretinal tissue, we investigated the presence of IGF-I receptor/binding protein in proliferating diabetic fibrovascular epiretinal membranes. Five fibrovascular epiretinal membranes were obtained by vitrectomy from five patients with proliferating diabetic retinopathy. The presence of IGF-I receptors was investigated by autoradiography using 125I-labeled IGF-I on frozen sections. To characterise binding specificity, some sections were preincubated with either insulin or unlabeled IGF-I. Sections of post-mortem liver were used as controls. Strong labeling of cells with 125I-labeled IGF-I was observed in all epiretinal membranes and in liver cells. Almost no autoradiographic labeling was observed in sections that had been blocked with non-radioactive IGF-I, and very little labeling was found following blockage with insulin. Our preliminary study suggests the presence of IGF-I receptor/binding protein in human diabetic epiretinal membranes. These results support the hypothesis that IGF-I may be involved in the formation of proliferative diabetic membranes.

Autoradiography↗

Development, repair and regeneration of the retinal pigment epithelium.

An overview is presented of the retinal pigment epithelium (RPE) cell in repair and regeneration. Changes in the RPE associated with repair activities have been described as metaplasia. However, evidence is presented to show that RPE cells do not become either fibroblasts or macrophages but merely adopt the appearance of these cell types in pathological conditions. The phenotypic alterations seem to be substrate-related. The fibroblast form predominates on two-dimensional substrates rich in fibronectin and in three-dimensional collagen matrices. The macrophage form seems to be associated with insubstantial or inadequate substrates such as the vitreous, photoreceptor debris and some cell surfaces. In altered circumstances the dedifferentiated RPE can rapidly revert to an epithelioid form. However, the regeneration of an effective RPE mosaic is more difficult and dependent on many factors including the size of the initial lesion, the condition of the basement area, the status of the neuroretina and the existing pathology in the eye. The importance for the regeneration of a normal functioning RPE of the cells being out of the cell cycle, establishing effective junctioning, reorganising their cytoskeleton and having the required adhesive balance with the basement membrane is emphasised.

Cell Adhesion↗

Cytokeratin-containing cells in proliferative diabetic retinopathy membranes.

Immunohistochemical techniques were used to investigate the relation between retinal pigment epithelial cells (RPE), traction retinal detachment (TRD) membranes, and combined traction rhegmatogenous retinal detachment (CTR) membranes in proliferative diabetic retinopathy. Seven CTR and five TRD membranes were obtained during closed microsurgery. Six of the seven CTR membranes and one of the five TRD membranes contained RPE. Eleven of the 12 diabetic membranes incorporated glial cells. The findings emphasise that the intravitreal membranes of proliferative diabetic retinopathy contain a diversity of cell types and indicate that RPE tend to contribute to CTR, rather than TRD, membranes. The histopathological appearance of CTR membranes is that of a hybrid between TRD and proliferative vitreo-retinopathy membranes.

Diabetic Retinopathy↗

Retinal and preretinal localisation of epidermal growth factor, transforming growth factor alpha, and their receptor in proliferative diabetic retinopathy.

A number of growth factors have been implicated in the development and perpetuation of preretinal fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR). The aim of this study was to determine the potential role of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and their receptor (EGF-R) in PDR development. Immunostaining for EGF, TGF-alpha, and EGF-R was compared between normal retina, PDR retina, and PDR preretinal membranes. Weak staining for EGF and EGF-R was observed throughout the neural retina from non-diabetic eyes while weak to moderate staining for TGF-alpha was observed in the ganglion cell layer and the inner and outer nuclear layers. In contrast, intense staining for EGF and TGF-alpha and moderate staining for EGF-R were observed throughout the PDR retina. Immunoreactivity for EGF, TGF-alpha, and EGF-R was seen in the majority of the 11 excised membranes studied and, though variable, was generally greater than that observed in normal retinas. These results suggest an autocrine/paracrine role for EGF, TGF-alpha, and EGF-R in PDR.

Diabetic Retinopathy↗

Inflammatory cells in proliferative vitreoretinopathy subretinal membranes.

BACKGROUND: The inflammatory cell content of subretinal membranes occurring in proliferative vitreoretinopathy (PVR) has not yet been well characterized. This study was undertaken to investigate the inflammatory cells present in PVR subretinal membranes. METHODS: Eight subretinal membranes obtained surgically from eyes with PVR complicating rhegmatogenous retinal detachment were studied immunohistochemically using the avidin-biotin complex technique and a panel of monoclonal and polyclonal antibodies. RESULTS: T lymphocytes were found in five of the eight subretinal membranes. CD4+ T cells were demonstrated in four and CD8+ T cells in one of the membranes. T cells bearing the interleukin 2 receptor were found in two of four membranes studied. Macrophages were found in four membranes. No B lymphocytes or neutrophils were demonstrated, and there were no significant deposits of complement or immunoglobulins. Expression of the MHC class II antigen HLA DR was consistently found in frozen specimens. Glial cells and retinal pigment epithelial cells also were present in the membranes, often adjacent to T cells, although overall no obvious relationship was found between glial or retinal epithelial cells and T cells. CONCLUSION: The findings indicate that T lymphocytes are present in PVR subretinal membranes and have the potential to interact with other cell types in the pathogenesis of this condition.

B-Lymphocytes↗

The extracellular matrix of reparative tissue in the vitreous: fibronectin production in proliferative diabetic retinopathy membranes.

In a preliminary investigation into the origins of the extracellular matrix glycoprotein fibronectin in proliferative diabetic retinopathy (PDR) membranes, four globes containing PDR membranes were subjected to in situ hybridisation and immunohistochemical studies. Fibronectin mRNA was found in PDR membrane cells in two of the four globes. The fibronectin-producing cells exhibited fibroblast-like or macrophage-like morphology. Occasional intraretinal macrophage-like cells which contained fibronectin mRNA were also observed in three of the eyes. Variable fibronectin immunoreactivity was observed in all the PDR membranes, while the fibronectin staining pattern in the underlying retina was similar to that reported for albumin in eyes with breakdown of the blood-retina barrier. The findings suggest that fibronectin in PDR membranes originates from both plasma-derived fibronectin and the membrane cells, and support the concept that extracellular matrix components play an important role in PDR membrane progression.

Aged↗

The pathology of abortive neovascular outgrowths from the retina.

Seven abortive neovascular outgrowths (ANVOs) from diabetic retinas were obtained for examination either by biopsy during pars plana vitrectomy (2) or after discovery within enucleated globes (5). Scanning and electron microscopical, histochemical, immunohistochemical and retinal digest techniques were used. The ANVOs consisted of nodules of vessels without an extravascular fibrous component. Two of them contained aneurysm-like dilatations of constituent vessels, and all the specimens showed gross hyaline thickening of the vessel walls. The vascular sclerosis was probably due to accumulation of plasma proteins in the walls of the damaged vessels, which contributes to their involution seen clinically after retinal photocoagulation.

Adult↗

Local production of fibronectin by ectopic human retinal cells.

The distribution of fibronectin mRNA and fibronectin in adult human retina and epiretinal membranes was investigated by in situ hybridisation and immunohistochemical techniques. The cells in normal adult retina contained little or no fibronectin mRNA and the retina only showed fibronectin immunoreactivity in retinal vessels. The cells in detached neuroretina did not contain fibronectin message but the vitreoretinal interface of the detached retina exhibited variable fibronectin immunoreactivity. Retinal glia, retinal pigment epithelium and fibroblast-like cells in membranes at the vitreoretinal juncture (epiretinal membranes) showed variable labelling with the fibronectin mRNA probe and all the membranes immunostained for fibronectin. No difference could be detected between membrane cell types in the intensity of labelling with the mRNA probe or for fibronectin immunoreactivity. The results indicate that cells in situ in attached and detached adult human retina do not produce fibronectin. Although fibronectin at the vitreoretinal juncture in retinal detachment is probably partly derived from plasma fibronectin resulting from breakdown of the blood-retinal barrier, ectopic retinal cells produce fibronectin and contribute to the glycoprotein epiretinal membranes.

Adolescent↗

Proliferative vitreoretinopathy. Lymphocytes in epiretinal membranes.

BACKGROUND: To investigate the potential contribution of inflammatory and immune-mediated processes contributing to the pathogenesis of proliferative vitreoretinopathy (PVR), an immunohistochemical study was undertaken to characterize the infiltrating inflammatory cells in epiretinal membranes surgically removed from the eyes of patients with PVR. METHODS: Twenty-one epiretinal membranes obtained surgically from eyes with PVR complicating rhegmatogenous retinal detachment were studied immunohistochemically using the ABC technique and a panel of monoclonal and polyclonal antibodies. RESULTS: T lymphocytes were found in 18 of the 21 specimens and generally constituted a small percentage of the total cell number. CD4+ T cells were found in 14 of the 18 membranes containing T cells. Three of six frozen membranes contained T cells that were positive for the interleukin-2 receptor. In 5 of 16 membranes studied, cells positive for the macrophage/monocyte marker were found. No B lymphocytes or neutrophils were identified, and there were no deposits of complement or immunoglobulins. Positive staining for the class II MHC antigen HLA-DR was found in 7 of the 21 membranes, a result that was more consistent in frozen than in fixed tissues. CONCLUSION: The study suggests that T lymphocytes are present in PVR epiretinal membranes and may be activated. These cells have the potential to play a role in the pathobiology of PVR.

Cell Membrane↗

Thrombospondin as a component of the extracellular matrix of epiretinal membranes: comparisons with cellular fibronectin.

We compared the distribution of the adhesive extracellular matrix glycoproteins thrombospondin and cellular fibronectin in epiretinal membranes. A total of nine membranes were investigated with immunohistochemical techniques. Thrombospondin and cellular fibronectin immunoreactivity were observed in seven of the specimens and immunostaining for the two glycoproteins was co-localised in four of the membranes. The findings indicate that thrombospondin contributes to the extracellular glycoprotein content of epiretinal membranes and is frequently co-distributed with cellular fibronectin in the tissue. As a consequence, thrombospondin may play a role in the assembly of the extracellular matrix of epiretinal membranes.

Diabetic Retinopathy↗

Fibronectin synthesis in subretinal membranes of proliferative vitreoretinopathy.

In situ hybridisation and immunohistochemical studies were conducted on six surgically excised subretinal membranes of proliferative vitreoretinopathy to investigate whether displacement of retinal pigment epithelial and glial cells to subretinal membranes was associated with fibronectin production by the subretinal membrane cells. Fibronectin messenger RNA (mRNA) and fibronectin immunoreactivity were observed in some cells in all of the subretinal membranes studied and up to 30% of the cells in individual specimens showed intense labelling for fibronectin mRNA. The results support the concept that the cells in subretinal membranes produce fibronectin. Locally produced fibronectin may play a role in subretinal membrane cohesion, and displacement of retinal pigment epithelial and glial cells from their normal location may induce the cells to manufacture fibronectin. Fibronectin production may be more prominent in migrating subretinal cells.

Eye Diseases↗

Oxytalan fibres in proliferative vitreoretinopathy.

The distribution of elastic and related fibres was studied in 29 fibrocellular membranes associated with proliferative vitreoretinopathy using histochemical, immunohistochemical and ultrastructural techniques. Ten subretinal and ten epiretinal membranes were subjected to light microscopical investigation, whilst the remaining nine membranes were examined by transmission electron microscopy. Oxytalan fibres, an elastic fibre precursor that is found in a variety of normal and pathological connective-tissue matrices, were identified in all of the specimens. Mature elastic fibres were not observed in any of the 29 membranes. The demonstration that oxytalan connective-tissue fibres contribute to the infrastructure of PVR membranes adds further evidence to the suggestion that this proliferative tissue might be the result of a repair mechanism.

Adolescent↗