Inhibition of antiviral CTL responses by virus-infected cells: line item veto (cells) revisited.
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Animals↗
Biomedical subjects
W R Green
Publications and source records attributed to W R Green.
Acute unilateral corneal immunoprotein deposition in IgM monoclonal gammopathy.
A healthy 43-year-old officer of a merchant ship at sea developed pain, redness, and photophobia in his right eye. During the next 2 weeks, he noted the presence of a band of opacity spreading from his temporal limbus toward his central cornea. His episcleral vessels were engorged in a distribution contiguous with the peripheral, sectorial, fleck-like corneal opacities. The opacity had progressed during topical and systemic antibiotic therapy, but halted with use of topical corticosteroids. Systemic evaluation showed mild IgM monoclonal gammopathy. Transmission electron microscopy of a corneal biopsy specimen revealed electron-dense fibrils identified as immunoprotein. To our knowledge, this is the first report of a case of acute unilateral deposition of corneal immunoprotein in a patient with monoclonal gammopathy. Clinicians should begin with a broad differential diagnosis when evaluating patients with corneal opacity.
Acute Disease↗
Repopulation of denuded murine Descemet's membrane with life-extended murine corneal endothelial cells as a model for corneal cell transplantation.
BACKGROUND: Corneal endothelial cell transplantation has been an intriguing concept as an alternative to full-thickness penetrating keratoplasty. Using a murine corneal transplantation model, we sought to establish the optimal conditions to repopulate, ex vivo, denuded murine Descemet's membrane with life-extended cell cultures of murine corneal endothelial cells. These ex vivo repopulated corneas were used as donor corneas in a murine orthotopic corneal transplantation model to assess, in vivo, the function of the transplanted, life-extended murine corneal endothelial cells (MCEC). METHODS: Mouse corneas were surgically trephined and the native corneal endothelium was removed mechanically using a sterile cotton swab. Cultured murine corneal endothelial cells (life extended by expression of the SV40 large T antigen) were added onto the denuded Descemet's membrane and allowed to attach in culture at 37 degree C. Evidence of corneal cell attachment to Descemet's membrane was determined between 1 and 8 h by scanning and transmission electron microscopy. Donor life-extended corneal endothelial cells were labeled with a fluorescent dye to allow tracking of the donor cells following seeding onto denuded Descemet's membrane. In four independent experiments, the Descemet's repopulated corneas were placed into syngeneic mice and evaluated for corneal clarity after 6 weeks. RESULTS: We could detect attachment of the life-extended murine CEC by scanning and transmission electron microscopy to denuded Descemet's membrane. The optimal time for adherence was 2 h and these repopulated corneas were used as donors in a murine model of penetrating keratoplasty. Of 20 mice evaluated after 6 weeks, 4 displayed corneal clarity, and fluorescent evaluation demonstrated that only the donor corneal endothelial cells were present. CONCLUSIONS: This experimental protocol establishes that "life-extended" MCEC can bind to Descemet's membrane ex vivo and form a distinct monolayer. The repopulated Descemet's membrane allowed us to directly test the hypothesis that cultured life-extended corneal endothelial cells are functional when reintroduced into an in vivo milieu and provides evidence that specific corneal endothelial cell transplantation may be a viable alternative to pentrating keratoplasty.
Animals↗
Surgical management of recurrent iris stromal cyst.
PURPOSE: To report the clinical history and surgical management of recurrent congenital iris stromal cyst. METHOD: Case report. Argon laser endophotocoagulation and cryotherapy were used to treat a recurrent iris stromal cyst in an 18-month-old boy. RESULTS: At 43 months of follow-up, there was no recurrence or evidence of epithelial ingrowth. CONCLUSION: Treatment with argon laser endophotocoagulation and cryotherapy resulted in complete resolution of a recurrent congenital iris cyst.
Cryotherapy↗
Use of topical cyclosporin for conjunctival manifestations of actinic prurigo.
PURPOSE: To report the successful treatment of conjunctival manifestations of actinic prurigo with topical cyclosporin. METHODS: A 12-year-old female with extensive limbal lesions and chronic conjunctivitis secondary to actinic prurigo was treated with topical cyclosporin, and a rapid clinical response was observed. RESULTS: The patient had the limbal lesions surgically excised. The lesions completely recurred over the first 2 postoperative months. Treatment with topical steroids and vitamin A ointment was unsuccessful. The patient was then treated with cyclosporine 2% drops and a dramatic improvement occurred. Over a 3-month period, the lesions completely resolved. CONCLUSION: Cyclosporine eyedrops may be an effective treatment for the conjunctival manifestations of actinic prurigo.
Administration, Topical↗
Ocular histopathologic study of a patient with the T 8993-G point mutation in Leigh's syndrome.
OBJECTIVE: To report the histopathologic findings of eyes from a patient with Leigh's syndrome associated with the T 8993-G point mutation in mitochondrial DNA (mtDNA). DESIGN: Case report. INTERVENTION: A child with hypotonia, developmental delay, persistent lactic acidosis, seizures, and ataxia died of aspiration pneumonia at 15 months of age. Analysis of DNA isolated from blood was positive for the T to G point mutation at position 8993 in mtDNA, and the proportion of mutant genomes was estimated at approximately 95%. The type and distribution of abnormalities seen in the brain at autopsy were consistent with those in patients with Leigh's syndrome. MAIN OUTCOME MEASURES: The left eye was examined by light microscopy, and segments of the right eye were examined by transmission electron microscopy. Genetic analysis on DNA isolated from blood was performed. RESULTS: Thinning of the nerve fiber and ganglion cell layers was present in the nasal aspect of the macula, and mild atrophy of the temporal aspect of the optic nerve head and optic nerve was present. Electron microscopic study disclosed numerous distended mitochondria in all cells, but particularly in the retinal pigment epithelium, nonpigmented ciliary epithelium, and corneal endothelium. CONCLUSION: This is a report of the ocular histopathologic findings in Leigh's syndrome with the T 8993-G point mutation. The light microscopic findings were similar to those of patients with similar features reported previously. In addition, ultrastructural abnormalities of mitochondria were present.
Ciliary Body↗
Band-shaped and whorled microcystic dystrophy of the corneal epithelium.
OBJECTIVE: To report the clinical, histopathologic, and electron microscopic features of band-shaped and whorled microcystic corneal epithelial dystrophy. DESIGN: Two interventional case reports. PARTICIPANTS: Two patients, two eyes. INTERVENTION: The involved area of corneal epithelium was scraped from each cornea. RESULTS: Histopathologic examination showed microscopic vacuoles in the epithelial cytoplasm in both cases. Electron microscopic examination revealed mainly empty cytoplasmic vacuoles with scant nonspecific osmophilic material. The process recurred clinically in one patient. Changes in corneal topography are documented in one patient. CONCLUSION: Clinical findings and pathologic studies seem nearly identical to those in the original report. No pattern of systemic disorder or medication use was found. The cause of this condition remains unknown.
Aged↗
Adult-onset foveomacular pigment epithelial dystrophy: clinicopathologic correlation of three cases.
PURPOSE: The authors describe the clinicopathologic features of three patients with adult onset foveomacular pigment epithelial dystrophy (AOFPED). METHODS: The eyes of three patients were studied ophthalmoscopically and by fluorescein angiography, and obtained postmortem and studied by light and electron microscopy. RESULTS: Histopathologic study of the three patient's eyes disclosed central loss of the retinal pigment epithelium and photoreceptor cell layer with a moderate number of pigment-containing macrophages present in the subretinal space and outer retina. To either side, the retinal pigment epithelium was distended with much lipofuscin. Basal laminar and basal linear deposits were present throughout the central area. No discontinuities of Bruch membrane were present. CONCLUSION: The findings in the eyes of three patients with AOFPED included marked aging changes that are similar to those seen in age-related macular degeneration. Pigmented cells with lipofuscin in the subretinal space account for the vitelliform appearance.
Age of Onset↗
Naturally occurring TAP-dependent specific T-cell tolerance for a variant of an immunodominant retroviral cytotoxic T-lymphocyte epitope.
Upon immunization and restimulation with tumors induced by the endogenous AKR/Gross murine leukemia virus (MuLV), C57BL/6 mice generate vigorous H-2K(b)-restricted cytotoxic T-lymphocyte (CTL) responses to a determinant (KSPWFTTL) derived from the p15E transmembrane portion of the viral envelope glycoprotein. By contrast, the highly homologous determinant RSPWFTTL, expressed by tumor cells induced by Friend/Moloney/Rauscher (FMR) MuLV, is not immunogenic, even when presented to the immune system as vaccinia virus-encoded cytosolic or endoplasmic reticulum (ER)-targeted minigene products. Such minigene products are usually highly immunogenic since they bypass the need for cells to liberate the peptide or transport the peptide into the ER by the transporter associated with antigen processing (TAP). Using KSPWFTTL-specific CTLs that cross-react with RSPWFTTL, we previously demonstrated that presentation of RSPWFTTL from its natural viral gene product is TAP dependent. Here, we show first that C57BL/6 mice express mRNA encoding RSPWFTTL but not KSPWFTTL and second that the ER-targeted RSPWFTTL minigene product is highly immunogenic in C57BL/6 mice with a targeted deletion in TAP1. These findings provide the initial demonstration of TAP-dependent tolerance induction to a specific self peptide and demonstrate that this contributes to the differential recognition of RSPWFTTL and KSPWFTTL by C57BL/6 mice.
ATP-Binding Cassette Transporters↗
Histologic correlation of human neural retinal transplantation.
PURPOSE: To describe the histologic findings of the transplanted eye of a 94-year-old man with neovascular age-related macular degeneration, who 3 years earlier underwent subretinal transplantation of both a fetal neural retinal sheet and a retinal microaggregrate suspension. METHODS: Serial sections of the posterior segment of the eye and the transplanted areas were processed and studied by routine histologic techniques, including both light and transmission electron microscopy (TEM). Transplanted areas were also examined for the presence of glial, neuronal, and photoreceptor cell markers by standard immunohistochemical methods. RESULTS: After transplantation in this patient, there was no visual improvement. Light microscopic examination disclosed survival of the transplanted cells in the subretinal space with no evidence of inflammation or rejection. The neural retinal sheet transplant developed a layered configuration. The retinal pigment epithelium (RPE) was absent over much of the posterior pole, including the area of transplantation. TEM examination and immunohistochemical analysis disclosed the presence of neuronal and glial cells within the transplant. A few transplant neuronal cell processes overlying a focus of residual RPE cells were positive for S-antigen, but well-developed photoreceptor outer segments were not present. CONCLUSIONS: Long-term survival of transplanted neural retinal tissue can be achieved in human patients without immunosuppression. The lack of photoreceptor development in this patient may be the result of absent or dysfunctional RPE. Nonetheless, the long-term survival of grafted tissue in the human subretinal space in the absence of immunosuppressive treatment is promising for future efforts in the field of neural retinal transplantation.
Aged↗
Histopathologic studies of ischemic optic neuropathy.
PURPOSE: To define the histopathologic features of eyes in which a pathologic diagnosis of ischemic optic neuropathy had been made in the years 1951 through 1998. METHODS: The following data were documented: age of patient, race, sex, source of tissue, cause of death, clinical history, interval from loss of vision to death, enucleation, exenteration, and biopsy. The histopathologic criteria for diagnosis of ischemic optic neuropathy were the presence of localized ischemic edema, cavernous degeneration, or an area of atrophy located superior or inferior in the optic nerve. Cases with history of abrupt loss of vision were combined with reports from the literature to construct a time table of histopathologic features and associated conditions. RESULTS: Ischemic optic neuropathy was present in 193 eyes. There were 88 females and 65 males. The average age was 71.6 years. Ischemic edema without (early) and with (later) gitter macrophages was present in 26 (13.5%). Cavernous degeneration was present in 69 nerves (36%). Mucopolysaccharide (MPS) was present in 37 cavernous lesions 1 month or longer after loss of vision. Cavernous lesions were seen in 3 eyes in which peripapillary retinal nerve fiber layer hemorrhage had been observed prior to death. Atrophic lesions, the most common pattern, were observed in 133 optic nerves (66.8%). More than 1 ischemic lesion was seen in 38 optic nerves (19.7%). Bilateral ischemic lesions were seen in 50 (35.2%) of 142 paired eyes. CONCLUSIONS: Ischemic optic nerve lesions are initially acellular and later show macrophage infiltration. Cavernous lesions with MPS are present 4 weeks or longer after vision loss. The location of MPS posteriorly and along the internal margin suggests that MPS is produced at the edges of lesions. Progressive vision loss in ischemic optic neuropathy may be secondary to compression of intact nerve from ischemic edema and cavernous swelling, or a second ischemic lesion.
Aged↗
Histopathology of age-related macular degeneration.
Age-related macular degeneration is a diffuse condition involving the retinal pigment epithelium, the photoreceptor cell layer, and perhaps the choriocapillaris. The early morphologic change is the development of basal deposits of two distinct types. This phase is not ophthalmoscopically detectable but psychophysical testing may demonstrate reduced function. The process becomes detectable with the occurrence of secondary changes in the pigment epithelium, soft drusen formation, and choroidal neovascularization. A reparative response results in disciform scars. The various morphologic forms of age-related macular degeneration are interrelated.
Choroidal Neovascularization↗
Histopathological features of vitreous removed at macular hole surgery.
OBJECTIVE: To describe the histopathological features of the vitreous removed at surgery for macular holes in 200 consecutive cases. METHODS: The complete vitrectomy specimen in each case was concentrated by means of cellulose membrane filters and stained for light microscopy. The cases were organized into 5 categories: (1) all cases (N = 200), (2) eyes without previous vitrectomy (n = 174), (3) eyes with previous vitrectomy (n = 26), (4) idiopathic cases (n = 143), and (5) traumatic (accidental or surgical) cases (n = 31). The type and frequency of tissue fragments present in the vitreous were determined for each case. RESULTS: Fibrocellular and cellular membrane fragments were found in a minority of cases in all categories. Retinal fragments were a rare finding, present in only 4 cases. Inflammation was present in 57 (28.5%) of all cases. CONCLUSIONS: The absence of fibrocellular and cellular membrane fragments in the majority of cases suggests that mechanisms other than cellular proliferation are important in the pathogenesis of macular holes. These fragments are, however, the likely histopathological correlate of the opercula that are often observed clinically in patients with macular hole. Opercula rarely if ever contain retinal fragments, and thus are better termed pseudo-opercula, as has been previously suggested. The cellular proliferation and inflammation that are observed in some of the cases are likely a secondary or reactive process.
Aged↗
Pars plana vitrectomy and subretinal surgery for ocular toxocariasis.
The clinical course of ocular toxocariasis and the chronological development of peripheral retinal and macular granulomas are reported. Removing the epiretinal as well as subretinal component of the granuloma via pars plana vitrectomy and retinotomy techniques yielded an excellent clinical result. Clinicopathologic correlation of the specimen confirmed the diagnosis with histological evidence of degenerated larval structures in granulomatous inflammation.
Animals↗
VHL gene deletion and enhanced VEGF gene expression detected in the stromal cells of retinal angioma.
OBJECTIVE: Retinal angioma frequently occurs in von Hippel-Lindau (VHL) disease. However, VHL gene alterations have not been documented in retinal angiomas. METHODS: Using tissue microdissection and polymerase chain reaction amplification, we have analyzed 7 retinal angiomas associated with VHL disease for loss of heterozygosity of the VHL gene. In addition, vascular endothelial growth factor expression was evaluated in these tumors by immunohistochemistry and in situ hybridization. RESULTS: All 6 informative retinal angiomas showed loss of heterozygosity of the VHL gene. Loss of heterozygosity was detected in vacuolated "stromal" cells, but not in vascular cells or reactive glial tissue. Vascular endothelial growth factor protein and messenger RNA were also present in vacuolated "stromal" cells. CONCLUSIONS: These findings suggest that vacuolated "stromal" cells represent the true neoplastic component in retinal angioma. These cells express vascular endothelial growth factor and therefore may be responsible for abundant neovascularization of retinal angioma.
Adult↗
True exfoliation of the lens capsule.
True exfoliation or lamellar delamination of the lens capsule is a rare disorder in which the lens capsule is thickened and the superficial portion of the lens capsule splits from the deeper layer and extends into the anterior chamber. The pathogenesis of this disorder is not clear, but intense infrared radiation has been thought to be the main causative factor. We describe a patient with a history of heat exposure who had a cataract and was found to have bilateral delamination of the anterior lens capsule. Findings from light microscopy and scanning and transmission electron microscopy demonstrated a lamellar separation of the anterior portion of the lens capsule, confirming the diagnosis of true exfoliation.
Aged↗
Lytic Paget disease as a cause of orbital cholesterol granuloma.
A case of histologically confirmed Paget disease of the orbit produced a lesion that appeared both clinically and histologically similar to a cholesterol granuloma. This case is unique because of the unusual location of the lesion, its presentation in a patient with no other manifestations of Paget disease, and the histological picture produced by the disease.
Cholesterol↗