53 research outputs found
Herpes simplex virus-specific T cells infiltrate the cornea of patients with herpetic stromal keratitis: no evidence for autoreactive T cells
PURPOSE: Herpetic stromal keratitis (HSK) is a T-cell-mediated
inflammatory disease initiated by a herpes simplex virus (HSV) infection
of the cornea. Recently, studies in the HSK mouse model have shown that
the immunopathogenic T cells are directed against the HSV protein UL6
cross-reacting with an unknown corneal autoantigen. Whether this type of
autoimmunity plays a role in human HSK was analyzed. METHODS: T-cell lines
(TCLs) were generated from corneal buttons of 12 patients with different
clinical stages of HSV-induced necrotizing stromal keratitis (n = 9) or
immune stromal keratitis (n = 3). The initiating virus was identified by
polymerase chain reaction and immunohistology performed on the corneal
buttons. Peripheral blood mononuclear cells (PBMCs) were isolated, and B
cell lines (BLCLs) were generated by transformation with Epstein-Barr
virus. Proliferative responses of these intracorneal TCLs were determined
by culturing T cells with autologous BLCLs infected with HSV-1, HSV-2,
wild-type vaccinia virus (VV-WT), or VV expressing HSV-1 UL6 (rVV-UL6).
Alternatively, T cells were incubated with PBMCs pulsed with human cornea
protein extract. RESULTS: Irrespective of clinical diagnosis or treatment,
T cells were recovered from the corneal buttons of all the 12 HSK
patients. The intracorneal TCLs of 9 of the 12 HSK patients showed
HSV-specific T-cell reactivity. In none of the TCLs, T-cell reactivity
against HSV-1 UL6 or human corneal antigens was detected. CONCLUSIONS:
These data suggest that the potentially immunopathogenic intracorneal
T-cell response in HSK patients is directed to the initiating virus and
not to a human corneal autoantigen or HSV-1 UL6
Adhesion molecules in iris biopsy specimens from patients with uveitis
BACKGROUND/AIMS: Earlier studies on intraocular tissue have demonstrated
that T lymphocytes play a major role in the pathogenesis of uveitis.
Adhesion molecules are immunoregulatory molecules for the interaction
between T lymphocytes and vascular endothelium and they play an important
role in the recruitment of specific T lymphocytes from the circulation
into inflamed tissue. In uveitis an increased expression of some of these
adhesion molecules may be expected. METHODS: The presence of adhesion
molecules was investigated in iris biopsy specimens from 11 patients with
uveitis and eight controls (patients with primary open angle glaucoma)
immunohistochemically with a panel of monoclonal antibodies: LECAM (CD
62L), ICAM-1 (CD 54), LFA-1 (CD 11a/18), VCAM-1 (CD 106), VLA-4 (CD 49d),
and HECA-452, a marker for high endothelial venules. RESULTS: Positive
staining for ICAM-1, LFA-1 and VCAM-1 was found in the iris in a
significantly higher number of uveitis patients than in controls. The
remaining adhesion molecules were also found in a higher number of uveitis
patients than in controls, but this difference did not reach statistical
significance. CONCLUSION: An increased expression of adhesion molecules
was found in the iris of patients with uveitis, indicating an
immunoregulatory function for adhesion molecules in the pathogenesis of
uveitis
Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration
PURPOSE: The growth of ocular neovascularization is regulated by a balance
between stimulating and inhibiting growth factors. Somatostatin affects
angiogenesis by inhibiting the growth hormone-insulin-like growth factor
axis and also has a direct antiproliferative effect on human retinal
endothelial cells. The purpose of our study is to investigate the
expression of somatostatin receptor (sst) subtypes and particularly sst
subtype 2A (sst2A) in normal human macula, and to study sst2A in different
stages of age-related maculopathy (ARM), because of the potential
anti-angiogenic effect of somatostatin analogues. METHODS: Sixteen eyes
(10 enucleated eyes, 4 donor eyes, and 2 surgically removed choroidal
neovascular [CNV] membranes) of 15 patients with eyes at different stages
of ARM were used for immunohistochemistry. Formaldehyde-fixed
paraffin-embedded slides were incubated with a polyclonal anti-human sst2A
antibody. mRNA expression of five ssts and somatostatin was determined in
the posterior pole of three normal human eyes by reverse
transcriptase-polymerase chain reaction. RESULTS: The immunohistochemical
expression of sstA in newly formed endothelial cells and fibroblast-like
cells was strong in fibrovascular CNV membranes. mRNA of sst subtypes 1,
2A, and 3, as well as somatostatin, was present in the normal posterior
pole; sst subtypes 4 and 5 were not detectable. CONCLUSIONS: Most
early-formed CNV in ARM express sst2A. The presence of mRNA of sst subtype
2A was observed in normal human macula, and subtypes 1 and 3 and
somatostatin are also present. sst2A receptors bind potential
anti-angiogenic somatostatin analogues such as octreotide. Therefore,
somatostatin analogues may be an effective therapy in early stages of CNV
in ARM
Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration
PURPOSE: The growth of ocular neovascularization is regulated by a balance
between stimulating and inhibiting growth factors. Somatostatin affects
angiogenesis by inhibiting the growth hormone-insulin-like growth factor
axis and also has a direct antiproliferative effect on human retinal
endothelial cells. The purpose of our study is to investigate the
expression of somatostatin receptor (sst) subtypes and particularly sst
subtype 2A (sst2A) in normal human macula, and to study sst2A in different
stages of age-related maculopathy (ARM), because of the potential
anti-angiogenic effect of somatostatin analogues. METHODS: Sixteen eyes
(10 enucleated eyes, 4 donor eyes, and 2 surgically removed choroidal
neovascular [CNV] membranes) of 15 patients with eyes at different stages
of ARM were used for immunohistochemistry. Formaldehyde-fixed
paraffin-embedded slides were incubated with a polyclonal anti-human sst2A
antibody. mRNA expression of five ssts and somatostatin was determined in
the posterior pole of three normal human eyes by reverse
transcriptase-polymerase chain reaction. RESULTS: The immunohistochemical
expression of sstA in newly formed endothelial cells and fibroblast-like
cells was strong in fibrovascular CNV membranes. mRNA of sst subtypes 1,
2A, and 3, as well as somatostatin, was present in the normal posterior
pole; sst subtypes 4 and 5 were not detectable. CONCLUSIONS: Most
early-formed CNV in ARM express sst2A. The presence of mRNA of sst subtype
2A was observed in normal human macula, and subtypes 1 and 3 and
somatostatin are also present. sst2A receptors bind potential
anti-angiogenic somatostatin analogues such as octreotide. Therefore,
somatostatin analogues may be an effective therapy in early stages of CNV
in ARM
Detection of genetic prognostic markers in uveal melanoma biopsies using fluorescence in situ hybridization
PURPOSE: In uveal melanoma, specific chromosomal abnormalities are known
to correlate with the risk of metastases; changes in chromosomes 3 and 8q
correlate strongly with a decreased survival of the patient, whereas
chromosome 6 abnormalities are associated with a better prognosis.
Usual
Autologous peripheral retinal pigment epithelium translocation in patients with subfoveal neovascular membranes
AIM: To evaluate the possibility of translocating autologous peripheral
retinal pigment epithelial (RPE) cells and enhance their adhesion to
improve functional outcome after choroidal neovascular membrane extracti
The molecular products and biogeochemical significance of lipid photooxidation in West Antarctic surface waters
The seasonal depletion of stratospheric ozone over the Southern Hemisphere allows abnormally high doses of ultraviolet radiation (UVR) to reach surface waters of the West Antarctic Peninsula (WAP) in the austral spring, creating a natural laboratory for the study of lipid photooxidation in the shallow mixed layer of the marginal ice zone. The photooxidation of lipids under such conditions has been identified as a significant source of stress to microorganisms and short-chain fatty acids altered by photochemical processes have been found in both marine aerosols and sinking marine particle material. However, the biogeochemical impact of lipid photooxidation has not been quantitatively compared at ecosystem scale to the many other biological and abiotic processes that can transform particulate organic matter in the surface ocean. We combined results from field experiments with diverse environmental data, including high-resolution, accurate-mass HPLC-ESI-MS analysis of lipid extracts and in situ measurements of ultraviolet irradiance, to address several unresolved questions about lipid photooxidation in the marine environment. In our experiments, we used liposomes—nonliving, cell-like aggregations of lipids—to examine the photolability of various moieties of the intact polar diacylglycerol (IP-DAG) phosphatidylcholine (PC), a structural component of membranes in a broad range of microorganisms. We observed significant rates of photooxidation only when the molecule contained the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). As the DHA-containing lipid was oxidized, we observed the steady ingrowth of a diversity of oxylipins and oxidized IP-DAG; our results suggest both the intact IP-DAG the degradation products were amenable to heterotrophic assimilation. To complement our experiments, we used an enhanced version of a new lipidomics discovery software package to identify the lipids in water column samples and in several diatom isolates. The galactolipid digalactosyldiacylglycerol (DGDG), the sulfolipid sulfoquinovosyldiacylglycerol (SQDG) and the phospholipids PC and phosphatidylglycerol (PG) accounted for the majority of IP-DAG in the water column particulate (≥0.2 µm) size fraction; between 3.4 and 5.3% of the IP-DAG contained fatty acids that were both highly polyunsaturated (i.e., each containing ≥5 double bonds). Using a broadband apparent quantum yield (AQY) that accounted for direct and Type I (i.e., radical-mediated) photooxidation of PUFA-containing IP-DAG, we estimated that 0.7 ± 0.2 µmol IP-DAG m−2 d−1 (0.5 ± 0.1 mg C m−2 d−1) were oxidized by photochemical processes in the mixed layer. This rate represented 4.4% (range, 3–21%) of the mean bacterial production rate measured in the same waters immediately following the retreat of the sea ice. Because our liposome experiments were not designed to account for oxidation by Type II photosensitized processes that often dominate in marine phytodetritus, our rate estimates may represent a sizeable underestimate of the true rate of lipid photooxidation in the water column. While production of such diverse oxidized lipids and oxylipins has been previously observed in terrestrial plants and mammals in response to biological stressors such as disease, we show here that a similar suite of molecules can be produced via an abiotic process in the environment and that the effect can be commensurate in magnitude with other ecosystem-scale biogeochemical processes
Immunohistochemical Analysis of Iris Biopsy Specimens From Patients With Fuchs' Heterochromic Cyclitis
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