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Biomedical subjects

I H Wallow

Publications and source records attributed to I H Wallow.

At least 37 records · Page 2Linked to original sources

Immunocytochemical study of an eye with proliferative vitreoretinopathy and retinal tacks.

After an eye-wall resection for a choroidal melanoma, a 32-year-old woman had subsequent retinal detachment with proliferative vitreoretinopathy (PVR), and an unsuccessful attempt at repair with retinal tacks. Gross and light-microscopic examination of the globe revealed a total retinal detachment with extensive preretinal and subretinal membranes. The membranes surrounded the tack heads and extended in taut bands to form a tractional detachment of the pars plana. The membranes contained glial and nonglial cells. The glial cells immunolabeled for glial fibrillary acidic protein (GFAP), carbonic anhydrase-C (CA-C), vimentin, and glutamine synthetase (GS), thus suggesting that they were Müller's cells. While the tacks did not seem to cause PVR, in this case they may have provided an anchoring point from which membranes were able to exert traction on the retina and pars plana.

Adult↗

Immunostaining of preretinal membranes for actin, fibronectin, and glial fibrillary acidic protein.

The frequency and extent of immunostaining for actin, fibronectin (FN), and glial fibrillary acidic protein (GFAP) were determined in 37 preretinal membranes (PRMs) obtained at vitrectomy from 35 patients with proliferative diabetic retinopathy (PDR) (n = 16), proliferative vitreoretinopathy (PVR) (n = 18), or idiopathic macular pucker (MP) (n = 3). All three proteins were detected in the vast majority of specimens (actin, 86%; FN, 95%; GFAP, 96%), although the extent of staining varied for each. Actin-FN co-localization was observed in all diagnostic groups on comparison of adjacent sections and in double-labeled sections. The extent of actin staining did not correlate with clinical grading of PRM contraction. In PDR membranes, FN staining was low overall, but proportional to the vascular content of the PRM. Fibronectin staining of PVR membranes was greater, and extensive even in avascular specimens. In MP membranes, most cells were GFAP-positive, whereas in PDR and PVR specimens, GFAP staining was variable. The lack of correlation of clinical contractility and membrane composition, as studied in this article by immunostaining, indicates that other factors must play significant roles in determining membrane behavior.

Actins↗

The development of vitreous membranes and retinal detachment induced by intravitreal carbon microparticles.

We induced intravitreal cellular proliferation by injection of carbon microparticles (size 20-70 nm) into the vitreous of 21 eyes of 11 cynomolgus monkeys. Pathological changes were evaluated by light and electron microscopy. At 1 week, there was conspicuous cyclitis showing exudative separation of the nonpigmented and pigmented ciliary epithelium, inflammatory cells, mononuclear phagocytes, and premacular vitreous detachment. At 3 weeks, continued macrophagic response was accompanied by fibrovascular proliferation with ingrowth of vessels from the ciliary body into the vitreous. At 4-5 weeks, deposition of extracellular fibrous material and traction retinal detachment (RD) were found. At 10 weeks, all eyes had extensive RD with pre- and subretinal collagenous cellular membranes. Carbon-laden macrophages were aggregated over the optic disc and fovea with prepapillary neovascularization and cystoid macular edema. Thus, intravitreal fibrovascular proliferation, vitreous contraction, and RD were induced by inflammatory and phagocytic response to carbon particles.

Animals↗

Cystoid macular degeneration in experimental branch retinal vein occlusion.

Macular edema and collateral vessels were examined clinically and histopathologically up to 48 months after branch retinal vein occlusion in six eyes of five cynomolgus monkeys. In all six, central macular swelling and fluorescein leakage from the retinal vasculature were confined to the acute stage. However, histopathologically, at the chronic stage, only two maculas were completely recovered and unremarkable, whereas the other four showed variable degrees of cystoid degeneration and photoreceptor cell loss. In the two recovered maculas, six to eight normal-sized capillaries separated the fovea from the nearest cluster of capillary collaterals. In three maculas with cystic degeneration, collaterals incorporated the circumfoveal capillaries. In the fourth macula with cystic degeneration, collaterals were separated from the center by two normal-sized capillaries but were also associated with large areas of capillary nonperfusion partially due to occlusion of the macular arteriole.

Animals↗

Focal photocoagulation of diabetic macular edema. A clinicopathologic case report.

This is the first reported clinicopathologic correlation of focal photocoagulation treatment in a diabetic patient treated as part of the Early Treatment of Diabetic Retinopathy Study (ETDRS). Twenty focal argon laser burns were evaluated clinically in their acute and chronic stages, and histopathologically more than 3 years after exposure. Damage profiles of the lesions were reconstructed from serial tissue sections. In single burns the outer nuclear layer defect measured 78 +/- 31 microns, in confluent burns 257 +/- 73 microns. Inner nuclear layer defects were present only in lesions that clinically, during their acute stage, showed a white center or a white collar around the treated target. Fibrous subretinal and subpigment epithelial membranes extended from the burn centers for a distance of up to 900 microns and contained Müller cell processes as identified by immunostaining. These findings confirm the empirical rationale of current focal treatment, but also, because of the apparent risk of membrane formation, urge caution when treating close to the fovea.

Cadaver↗

Ocular renin-angiotensin: immunohistochemical evidence for the presence of prorenin in eye tissue.

Angiotensin II (A2) is a vasoconstrictor generated by the renin-angiotensin system. A2 appears to act also as an angiogenic factor. Recent evidence suggests that renin is synthesized at many tissue sites and may generate A2 locally. Local A2 may have important functions in the normal and diseased eye. We examined eight human eyes by immunostaining with an antibody to prorenin, the biosynthetic precursor of renin. In all eyes, prorenin staining was extensive in the pars plicata of the ciliary body suggesting that the ciliary body synthesizes renin and this renin may be part of an ocular A2 generating system.

Ciliary Body↗

Recessive dystrophic epidermolysis bullosa.

Recessive epidermolysis bullosa dystrophica (REBD), a bullous disorder of the skin and mucous membranes, is frequently associated with ocular complications. A 40-year-old woman presented with lid ulcerations, chronic conjunctivitis, diffuse subepithelial corneal scarring, corneal ulceration, and cataracts. Management with intensive lubricant therapy, soft-bandage contact lenses, and cataract extraction successfully restored her sight. Histologic examination via light and electron microscopy revealed blister formation and scarring beneath the epithelial basement membrane of both the skin and cornea, confirming the diagnosis of REBD. The ultrastructure of the skin and cornea and the ocular complications of the major forms of epidermolysis are described herein. To our knowledge, successful ocular management of a confirmed case of REBD with complete ocular histopathologic features has not been documented.

Adult↗

Müller's cell involvement in proliferative diabetic retinopathy.

To test whether the Müller's cell, and not the fibrous astrocyte alone, is an active glial element in proliferative diabetic retinopathy, we developed a method using enzyme histochemical analysis for carbonic anhydrase and immunolabelling for glial fibrillary acidic protein on plastic-embedded sections to detect Müller's cells in degenerated retinas. Four postmortem eyes with proliferative diabetic retinopathy were studied. Four features of Müller's cell behavior were observed: (1) Müller's cell nuclei migrated within the retina. (2) They were the principal glial cells in preretinal membranes. (3) Müller's cells formed horizontal bands, in the outer retina, that gave the appearance of subretinal membranes. (4) They formed intraretinal bridges between cystic spaces. In conclusion, the Müller's cell (or its progeny) plays an active role in proliferative diabetic retinopathy.

Adult↗

Microvascular changes in experimental branch retinal vein occlusion.

Collateral vessel maturation and regional capillary nonperfusion were examined clinically and histopathologically up to 48 months after branch retinal vein occlusion (BVO) in a monkey model. Significant increases in endothelial density, but not pericyte density, were noted in both dilated and normal capillary caliber vessels in regions of collateral flow, independent of duration of BVO from 4 to 15 1/2 months. Patent capillaries in regions of hypoperfusion showed increased endothelial densities but decreased pericyte densities. Pericyte loss was independent of duration of BVO; however, endothelial density may normalize years after BVO in these vessels.

Animals↗

The anatomy and histology of the anophthalmic socket--is the myofibroblast present?

For some anophthalmic patients, the contracted socket is a severe problem that precludes the wearing of a prosthesis. A normal and cosmetically acceptable appearance is dependent on the ability of a socket to retain a prosthesis. The disfigurement and distress caused by the contracted socket and its inability to accommodate a prosthesis may have a profound detrimental effect on the patient's career, self-esteem, and psychosocial interactions. The tissue dynamics at work in the anophthalmic socket and in the contracting socket are not yet understood. There are many unanswered questions regarding the histology and anatomy of the normal, as well as the contracting, socket. The tissue responsible for clinical contraction has not been identified. This thesis, using the cynomolgus monkey socket as an experimental model, investigated healing in both the normal and contracting socket. Qualitative observations of the anatomy and histology of eight sockets were made. Two of the sockets were treated with Croton oil to induce contractions. Biopsy specimens from two human sockets, one contracted and the other merely volume deficient, were also examined. Histopathology of the normal and contracting sockets were compared. Myosin subfragment 1 staining of actin for electron microscopy and immunoperoxidase staining of actin for light microscopy were performed on selected specimens. The myofibroblast, probably a modified fibroblast, is known to be present in the early stages of open wound healing and in contracting scar tissue elsewhere in the body. The myofibroblast has been incriminated as an agent generating contractile force. Under the conditions of this experiment, cells with the characteristics of myofibroblasts were identified by both immunoperoxidase staining and electron microscopy. They were found in healing noncontracting and contracting sockets. Cytoplasmic actin was also distinguished in arterioles, venules, capillaries, myoepithelial cells, smooth muscle, and skeletal muscle.

Actins↗

Fibronectin distribution in the rat eye. An immunohistochemical study.

Previous studies of fibronectin (FN) distribution in eye tissue have relied on immunofluorescence (IF) techniques on frozen sections, and have not included the rat. Using rat eyes, a technique was developed for immunoperoxidase (IP) staining of formalin fixed paraffin embedded material, and the results were compared to those obtained by IF. IP was technically more difficult, and required pepsinization of tissue after formalin fixation to obtain consistent results. The optimum pepsin time varied for different structures in the eye. IP offers better tissue preservation and stain resolution. Results with IF were consistent with those observed with the newly applied IP. The distribution of FN in rat eyes was similar though not identical to that reported in other species. Prominent stain was observed in the conjunctiva, basement membrane of the corneal epithelium, corneal stroma, anterior aspect of Descemet's membrane, trabecular meshwork, perivascular stroma of the ciliary body, choroid and retinal blood vessels. Lens structures, vitreous, and internal limiting membrane of the retina were negative.

Animals↗

HRP/trypsin technique for studies of the retinal vasculature.

The HRP/trypsin technique is a new histologic method for the light microscopic study of the retinal blood vessels. A two-stage procedure, the first step results in a retinal whole amount preparation which permits visualization of the three-dimensional architecture of perfused vessels and their relationship within the retina. This allows analysis of gross vessel morphology and differentiation of deep and superficial vascular beds. The second step involves digesting the whole mount with trypsin and staining with hematoxylin. This permits detailed evaluation of the density of retinal capillary endothelial cells and pericytes, recognition of basement membrane ghosts, microaneurysms, and other intraretinal microvascular abnormalities, with intravascular horseradish peroxidase as a perfusion marker. This technique has been employed with success in studies of the retinal vasculature in both normal and RCS rat retinas, and in a monkey model of branch retinal vein occlusion.

Animals↗

Subretinal new vessels after krypton laser photocoagulation.

The eye of a patient with age-related macular degeneration was treated with krypton laser photocoagulation and later studied histopathologically. Five months after treatment the original membrane was completely obliterated, but a separate new membrane was found, which was fed by the retinal circulation and not by the choroid. The frequency of such recurrences is not known, but they may be related to krypton laser treatment.

Aged↗

Comparison of superoxide generation and luminol-dependent chemiluminescence with eosinophils and neutrophils from normal individuals.

Although eosinophilia is found in many allergic and hypersensitivity diseases, the function of the eosinophil is not clearly established. To evaluate and characterize this function, anticoagulated blood from normal subjects was separated into purified populations of both eosinophils and neutrophils by a modified method for Percoll gradients. With this separation procedure, highly purified populations of eosinophils (95.0% +/- 2.1%) and neutrophils (97.2% +/- 0.4%) were obtained. Functional response of these two isolated granulocyte cell types was measured by luminol-dependent chemiluminescence (CL) and superoxide generation to opsonized zymosan and phorbol 12-myristate 13-acetate (PMA). Both the eosinophil and neutrophil peak CL response and superoxide generation to zymosan (1 mg), in the presence of autologous serum (10%), were identical. In contrast, when PMA (10(-4) to 10(0) micrograms/ml) was the stimulant, eosinophil CL was at least twofold greater than the neutrophil light emission (1,595,741 +/- 122,435 cpm/5 X 10(5) cells vs. 765,448 +/- 24,171 cpm/5 X 10(5) cells; n = 6). This same differential in responsiveness was seen in superoxide generation. Thus, under certain conditions the eosinophil's respiratory burst may be greater than that of the neutrophil, and this differential in metabolic activity may contribute directly to the eosinophil's inflammatory potential.

Cell Separation↗

Repair of the pigment epithelial barrier following photocoagulation.

Mild argon laser burns produced in the retina of cynomolgus monkeys underwent differentiated retinal repair with frequent restoration of the pigment epithelial barrier. Permeability of the restored barrier was tested by two tracers injected intravenously--horseradish peroxidase followed by electron microscopic evaluation and fluorescein sodium followed by fluorescence microscopic examination of freeze-dried tissue. Tightness of the barrier was associated with regularly arranged pigment epithelial cells joined by zonulae occludentes. Leakage of the barrier was associated with discontinuities in the line of regularly proliferated pigment epithelial cells. At times, the tracers stained the pigment epithelial cells diffusely but they did not accumulate in the subretinal space. Variable changes in the choriocapillaris were noted. Mild photocoagulation may be effective in treating central serous choroidopathy in man when restoration of the pigment epithelial barrier is stimulated.

Animals↗

Histopathology of focally photocoagulated preretinal new vessels.

The histopathologic effects of focal xenon arc and argon laser photocoagulation on three patches of preretinal new vessels were studied in a patient with proliferative diabetic retinopathy. Both treatment modalities achieved total obliteration of the vessels. However, the adjacent retina and choroid were severely damaged, and preretinal membranes were seen over all three patches. Local tissue destruction is minimized when preretinal neovascularization is treated indirectly by scatter photocoagulation. Currently, scatter photocoagulation is our treatment of choice.

Choroid↗