PubMed Health⌕ Search

Biomedical subjects

M Reza Dana

Publications and source records attributed to M Reza Dana.

At least 19 recordsLinked to original sources
PubMed2006

Keratocyte apoptosis and failure of corneal allografts.

BACKGROUND: Murine models of high-risk and low-risk corneal transplantation were used to determine the role of keratocyte apoptosis in the failure of orthotopic allogeneic corneal transplants. MATERIALS AND METHODS: Normal (low-risk, low-rejecting) and inflamed/vascularized (high-risk, high-rejecting) BALB/c recipient beds received fully mismatched C57BL/6 corneal allografts. Apoptosis was detected in the corneal stroma at various time points using an in situ terminal deoxynucleotide tranferase-mediated dUTP nick-end labeling assay, and ex vivo via Western analysis for active caspase-3. Apoptosis was also measured in a (donor-type) C57BL/6 keratocyte cell line after stimulation of Fas or via use of various pro-inflammatory cytokines. RESULTS: Significantly more apoptotic cells were present in the stroma of rapidly rejecting high-risk corneal allografts compared with low-risk grafts. Apoptotic cells were shown to be nearly uniformly CD45 and hence of a non-hematopoetic lineage. Apoptosis, however, was not present in highly inflamed but ungrafted corneas. Apoptosis was induced in keratocytes in vitro by dual stimulation with agonistic Fas mAb and either interleukin-1beta or tumor necrosis factor-alpha. CONCLUSION: Apoptosis of resident non-bone marrow-derived fibroblastic cells of the corneal stroma is strongly correlated with the failure of corneal allografts, particularly in the highly inflamed microenvironment of the high-risk allograft.

Animals↗
PubMed2006

Influence of aging on the polar and neutral lipid profiles in human meibomian gland secretions.

OBJECTIVE: To determine whether aging is associated with significant alterations in the polar and neutral lipid profiles in human meibomian gland secretions. METHODS: Meibomian gland secretions were collected from both eyes of younger and older men and women. Samples were processed for high-performance liquid chromatography or mass spectrometry and for the analysis of associated spectra of fragment ions. Subjects also underwent slitlamp evaluations of the eyelid. RESULTS: Aging is associated with numerous significant alterations in the lipid profiles of human meibomian gland secretions. Analysis of polar and neutral lipid patterns identified ions that were significantly different in secretions of younger vs older men and women, as well as ions that varied significantly only between men and women. Correlation coefficients within, but not between, groups were high. Aging was accompanied by increased opacity of meibomian gland secretions and by eyelid and eyelid margin changes. CONCLUSION: Aging is associated with significant sex-related alterations in the polar and neutral lipid profiles of human meibomian gland secretions. CLINICAL RELEVANCE: The observed changes may contribute to the age-related increase in the prevalence of dry eye syndromes.

Adult↗
PubMed2005

Early ocular chemokine gene expression and leukocyte infiltration after high-risk corneal transplantation.

PURPOSE: To determine the differential gene expression of chemokine species and leukocyte infiltration of grafts in the early pre-rejection postoperative period after high-risk (HR) compared to normal-risk (NR) corneal transplantation. METHODS: Fully mismatched and syngeneic corneal grafts were performed in NR (avascular) and HR (vascularized) recipient beds of BALB/c murine hosts. Gene expression levels of a panel of chemokines were determined by a multiprobe ribonuclease protection assay system. The profiles of infiltrating cells into the corneal grafts at the same times were determined immunohistochemically. RESULTS: Compared to NR transplantation, HR eyes exhibited significantly higher mRNA levels for macrophage inflammatory protein (MIP)-2 and monocyte chemotactic protein-1 (MCP-1) on day 1, and for eotaxin on days 1 and 3 after transplantation. By day 6 after transplantation, still well before graft rejection, significantly higher levels of RANTES, eotaxin, MIP-1alpha, MIP-1beta, MIP-2, and MCP-1 were detected in HR eyes. The overexpression of MIPs in HR eyes correlated with a significant increase in the number of infiltrating macrophages (p<0.01), and neutrophils (p<0.05) in HR compared to NR recipients. Low levels of eosinophil and mast cell infiltration were observed in all grafts, with a modest increase in mast cell infiltration (p<0.05) in HR compared to NR grafts. CONCLUSIONS: These results suggest that increased expression of gene products for select chemokines, in particular those that mediate recruitment of innate immune cells, in the early period after HR corneal transplantation is related to the enhanced leukocytic infiltration of grafts observed in HR keratoplasty.

Animals↗
PubMed2005

Acute unilateral leukemic hypopyon in an adult with relapsing acute lymphoblastic leukemia.

PURPOSE: To report acute unilateral hypopyon uveitis as an initial presenting feature of relapsing acute lymphoblastic leukemia (ALL) in an adult patient. DESIGN: Observational case report. METHODS: Anterior chamber paracentesis was performed in a 56-year-old male presenting with treatment-resistant unilateral hypopyon while in the remission phase of ALL. RESULTS: Examination of the aqueous humor aspirate revealed presence of malignant cells compatible with the previous bone marrow biopsy and subsequent spinal tap results. CONCLUSIONS: Atypical hypopyon uveitis can be an indication of relapsing ALL, even in adults. Prompt anterior chamber aspiration is required for the correct diagnosis and subsequent treatment.

Anterior Chamber↗
PubMed2005

Spontaneous corneal hem- and lymphangiogenesis in mice with destrin-mutation depend on VEGFR3 signaling.

Lymphangiogenesis, the formation of new lymphatic vessels, is important for tumor metastasis and induction of immunity to peripheral antigens including organ transplants. We herein describe a novel mouse model of spontaneous, secondary lymphangiogenesis in the normally avascular cornea. corn1 mice, which suffer from a deletion in the gene encoding the cytoskeletal protein destrin, develop hemangiogenesis as well as spontaneous outgrowth of LYVE-1+++/CD31+ lymphatic vessels into the cornea starting at age 4 weeks. Corneal lymphangiogenesis is delayed in onset, is less intense, and regresses earlier compared with hemangiogenesis. Moreover, the lymphangiogenesis is preceded only by a mild recruitment of CD45+ inflammatory cells into the cornea. In contrast to mice with inflammation-induced hem- and lymphangiogenesis, corn1 mice do not develop breakdown of the blood-aqueous barrier. Finally, in this novel mouse model, a blocking anti-VEGFR3 antibody significantly inhibited not only lymph- but also hemangiogenesis. In summary, destrin deletion has differential effects on spontaneous hem- and lymphangiogenesis in the normally avascular cornea and represents a novel mouse model to study the mechanisms of lymphangiogenesis and to test the antihem- and antilymphangiogenic properties of known or new antiangiogenic agents.

Actin Depolymerizing Factors↗
PubMed2005

Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women.

BACKGROUND: Dry eye syndrome (DES) is a prevalent condition, but information on risk or protective factors is lacking. OBJECTIVE: We aimed to determine the association between the dietary intake and ratio of n-3 and n-6 fatty acids (FAs) and DES occurrence. DESIGN: Of the 39876 female health professionals in the Women's Health Study (WHS), 32470 women aged 45-84 y who provided information on diet and DES were cross-sectionally studied. We assessed FA intakes by using a validated food-frequency questionnaire and assessed DES by using self-reports of clinically diagnosed cases. Of the sample, 1546 (4.7%) subjects reported DES. We used logistic regression models to estimate the odds ratios (ORs) and 95% CIs to describe the relation of FA intake with DES. RESULTS: After adjustment for demographic factors, hormone therapy, and total fat intake, the OR for the highest versus the lowest quintile of n-3 FAs was 0.83 (95% CI: 0.70, 0.98; P for trend = 0.05). A higher ratio of n-6 to n-3 FA consumption was associated with a significantly increased risk of DES (OR: 2.51; 95% CI: 1.13, 5.58) for >15:1 versus <4:1 (P for trend = 0.01). In addition, tuna consumption [1 serving was 113 g (4 oz)] was inversely associated with DES (OR: 0.81; 95% CI: 0.66, 0.99 for 2-4 servings/wk; OR: 0.32; 95% CI: 0.13, 0.79 for 5-6 servings/wk versus < or =1 serving/wk; P for trend = 0.005). CONCLUSIONS: These results suggest that a higher dietary intake of n-3 FAs is associated with a decreased incidence of DES in women. These findings are consistent with anecdotal clinical observations and postulated biological mechanisms.

Aged↗
PubMed2005

CCR5 chemokine receptor mediates recruitment of MHC class II-positive Langerhans cells in the mouse corneal epithelium.

PURPOSE: To characterize the chemokines and chemokine receptors that mediate the effect of proinflammatory cytokines, interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, on the recruitment of MHC class II(+) Langerhans cells (LCs) in the corneal epithelium. METHODS: A standard model for corneal LC recruitment, application of cautery to the central corneal surface was used, and the differential gene expression levels of a panel of chemokines and chemokine receptors were determined by RNase protection assay. Chemokine receptor-knockout mice were used to evaluate the recruitment of MHC class II(+) LCs to the corneal epithelium. To determine the sensitivity of selected chemokines to IL-1 and TNF-alpha stimulation, the chemokine gene expression pattern was analyzed after blockade of IL-1 and TNF receptors. RESULTS: CCR1, -2, and -5 were overexpressed in corneas after cauterization. Topical administration of soluble TNF receptor I and IL-1 receptor antagonist, which abrogated corneal LC recruitment, significantly suppressed the gene transcription levels of the ligands of CCR1 and/or -5, regulated on activation normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta. The recruitment of major histocompatibility complex (MHC) class II(+) LC was significantly suppressed in CCR5(-/-) mice and blockade of RANTES and MIP-1beta, but not in CCR1(-/-), CCR2(-/-)/MIP-1alpha(-/-), or MIP-1alpha(-/-) mice. The evaluation of epithelial CD11c(+) LC cells by confocal microscopy revealed coexpression for CCR5 primarily among B7(-) (CD80(-)/CD86(-)) subsets of these LCs but not among the mature B7(+) subsets of CD11c(+) LCs. CONCLUSIONS: These data suggest that CCR5 plays a critical role in mediating recruitment and mobilization of MHC class II(+) LCs into the corneal epithelium. Targeting CCR5 and its ligands may be a new strategy for modulating immunity.

Animals↗
PubMed2005

The controlled-environment chamber: a new mouse model of dry eye.

PURPOSE: To develop a controlled-environment chamber (CEC) for mice and verify the effects of a low-humidity setting on ocular surface signs in normal mice. METHODS: Eight- to 12-week-old BALB/c mice were used in a controlled-environment chamber (CEC) where relative humidity (RH), temperature (T), and airflow (AF) are regulated and monitored. Mice were placed into the CEC and exposed to specific environmentally controlled conditions (RH = 18.5% +/- 5.1%, AF = 15 L/min, T = 21-23 degrees C) for 3, 7, 14, and 28 days. Control mice were kept in a normal environment (RH = 50%-80%, no AF, T = 21-23 degrees C) for the same duration. Aqueous tear production by means of the cotton thread test, corneal fluorescein staining (score, 0-15), and goblet cell density in the superior and inferior conjunctiva were measured by a masked observer. RESULTS: No statistically significant differences between the groups were found at baseline. Decreased tear secretion and increased corneal fluorescein staining were significantly present on day 3, 7, 14, and 28 in animals kept in the CEC. Goblet cell density was significantly decreased in the superior conjunctiva on day 7, and on day 3, 7, and 14 in the inferior conjunctiva in the CEC-kept mice compared with control animals. CONCLUSIONS: This study indicates that exposure of normal mice to a low-humidity environment in a CEC can lead to significant alterations in tear secretion, goblet cell density, and acquisition of dry eye-related ocular surface signs.

Air↗
PubMed2005

Novel expression and characterization of lymphatic vessel endothelial hyaluronate receptor 1 (LYVE-1) by conjunctival cells.

PURPOSE: Lymphatic vessel endothelial hyaluronic acid receptor (LYVE-1) is a newly discovered lymphatic-specific marker. To date, there is no report of its expression on conjunctival cells. The purpose of this study was to investigate the expression of LYVE-1 in normal conjunctiva, to phenotype LYVE-1+ cells, and to study changes in their expression levels during corneal inflammation. METHODS: Flat-mounted conjunctivae or cross sections of eyeballs were harvested from BALB/c mice (6-8 weeks of age) for immunofluorescent confocal microscopic studies. RESULTS: The data demonstrate, for the first time, that in addition to its expression on lymphatic vessels, LYVE-1 was expressed on CD45+, CD11b+, and CD31- conjunctival cells, indicating a bone-marrow-derived monocytic lineage. Surprisingly, the number of cells that expressed LYVE-1 decreased during corneal inflammation, in conjunction with ingrowth of lymphatics into the cornea. CONCLUSIONS: A new population of monocytic cells has been found to express LYVE-1 in normal conjunctiva. These cells that normally express LYVE-1 may act as a reservoir for lymphangiogenesis and cell recruitment when the immune system is challenged.

Animals↗
PubMed2004

Accumulated lead exposure and risk of age-related cataract in men.

CONTEXT: Low-level lead exposure may increase the risk for a number of chronic age-related diseases. Several studies have documented the presence of lead in lenses with cataract. The intrusion of lead into the lens may alter lens redox status and cause protein conformational changes that decrease lens transparency. OBJECTIVE: To determine the relationship of cumulative lead exposure with the development of cataract. DESIGN, SETTING, AND PARTICIPANTS: Tibial (cortical) and patellar (trabecular) bone lead levels were measured by K x-ray fluorescence between 1991 and 1999 in a subset of participants in the Normative Aging Study (NAS), a Boston-based longitudinal study of aging in men. Among the first 795 NAS participants to have bone lead levels measured, we reviewed eye examination data (collected routinely every 3-5 years) for the period after the bone lead measurements were taken. We limited the population to men aged 60 years and older who had sufficient eye examination information available (n = 642). Blood lead levels were also measured. MAIN OUTCOME MEASURES: Cataract assessment was done while masked to the lead level results. A participant was considered to have cataract if there was documentation for either eye of cataract surgery or a cataract graded clinically as 3+ or higher on a 4-point scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated as estimates of the magnitude and significance of the relationship of lead exposure with cataract, in logistic regression models. RESULTS: The mean age of the study participants was 69 years and cataract was identified in 122 men. The age-adjusted OR (95% CI) for cataract for men in the highest vs lowest quintile of tibia lead level was 2.68 (1.31-5.50). Further adjustment for pack-years of cigarette smoking, diabetes, blood lead levels, and intake of vitamin C, vitamin E, and carotenoids resulted in an OR of 3.19 (95% CI, 1.48-6.90). For patella lead level, there was an increased risk of cataract in the highest vs lowest quintile (OR, 1.88; 95% CI, 0.88-4.02), but the trend was not significant (P = .16). Blood lead levels, more indicative of short-term exposure levels, were not significantly associated with cataract (OR, 0.89; 95% CI, 0.46-1.72; P = .73). CONCLUSIONS: These epidemiological data suggest that accumulated lead exposure, such as that commonly experienced by adults in the United States, may be an important unrecognized risk factor for cataract. This research suggests that reduction of lead exposure could help decrease the global burden of cataract.

Aged↗
PubMed2004

Relevance of the direct pathway of sensitization in corneal transplantation is dictated by the graft bed microenvironment.

Corneal grafts were until recently considered entirely devoid of resident APCs, giving rise to the tenet that alloantigen recognition is mediated exclusively by the indirect (host APC-dependent) pathway. The recent discovery of a resident myeloid corneal dendritic cell population that is normally MHC class II(-) but can readily up-regulate class II expression during inflammation led us to hypothesize that under certain conditions the direct pathway of allosensitization becomes operative. To test this, corneal allotransplants were performed in either inflamed (high-risk (HR)) or uninflamed (low-risk (LR)) host beds in mice, and the frequencies of host T cells activated via the direct pathway were determined. We found that directly primed CD4(+) T cells were detected in the HR but not LR setting, and these cells displayed a clear Th1 phenotype by 2 wk after grafting. Moreover, the use of MHC class II knockout donor tissue led to significantly enhanced survival of HR but not LR allografts. Finally, we show that donor corneal APC demonstrate high expression of CD40, CD80, and CD86 costimulatory molecules when derived from HR but not LR grafts. These data are the first to report that a functional donor APC-dependent direct response is elicited in corneal transplant hosts when the graft bed is inflamed and underscore the relevance of the graft microenvironment in dictating the pathway of allosensitization.

Animals↗
PubMed2004

Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity.

There are no studies so far linking molecular regulation of lymphangiogenesis and induction of adaptive immunity. Here, we show that blockade of vascular endothelial growth factor receptor-3 (VEGFR-3) signaling significantly suppresses corneal antigen-presenting (dendritic) cell trafficking to draining lymph nodes, induction of delayed-type hypersensitivity and rejection of corneal transplants. Regulating the function of VEGFR-3 may therefore be a mechanism for modulating adaptive immunity in the periphery.

Animals↗
PubMed2004

Healing of perforating rat corneal incisions closed with photodynamic laser-activated tissue glue.

BACKGROUND AND OBJECTIVES: Laser-activated photodynamic biologic tissue glues may be useful for closing incisions in ophthalmology. We report on the use of two such preparations to close perforating corneal incisions in living rats. STUDY DESIGN/MATERIALS AND METHODS: A previously described preparation containing a covalent albumin-chlorin e6 (ce6) conjugate (bovine serum albumin (BSA)-ce6), and a novel mixture of albumin and Janus Green (BSA/JG), both activated with a 665-nm diode laser were used to glue mouse skin ex vivo. The optimized glues were then used to seal incisions in rat corneas and results were compared to control incisions. Rats were sacrificed at day 1, 7, and 14 and eyes tested for leaking pressure and examined histopathologically. RESULTS: One day after treatment eyes closed with BSA-ce6 had a leaking pressure (in mmHg) of 357 compared to 193 for control incisions (P<0.01); closure with BSA/JG gave a leaking pressure of 430 (P<0.05 compared to BSA-ce6, and P<0.001 compared to control). Histological examination showed eyes sealed with BSA/JG have less inflammation present than untreated eyes at 7 days. CONCLUSIONS: These data demonstrate that photodynamic laser activated tissue glues can be used to effectively seal corneal incisions in living animals without thermal damage or undue inflammation.

Adhesives↗
PubMed2004

Expression of vascular endothelial growth factor receptor-3 (VEGFR-3) on monocytic bone marrow-derived cells in the conjunctiva.

Vascular endothelial growth factor-3 (VEGFR-3), also known as Fms-like tyrosine kinase receptor 4 (FLT-4), was thought to be expressed exclusively on the lymphatic endothelium, high endothelial venules, and rarely on vascular endothelium. It plays a critical role in the development of lymphatics and cancer metastasis. Very recently, however, VEGFR-3 expression has been identified on dendritic cells (DCs) in the inflamed cornea, and related to the trafficking of these cells to lymphoid organs. The current study was performed to evaluate the expression of VEGFR-3 in the conjunctiva. The conjunctiva and limbus of normal and inflamed murine eyes were excised and stained for VEGFR-3. Immunofluorescence double staining for CD11b, CD11c, CD31, CD45, GR-1, CD3, CD80, LYVE-1 and class II major histocompatibility complex (MHC) antigen expression, using confocal microscopy, was performed to further phenotype the VEGFR-3+ cells. VEGFR-3 and LYVE-1 expression was observed on lymphatic, but not blood vessel, endothelium. In addition, we also detected expression of VEGFR-3 on non-endothelial CD45+ bone marrow-derived cells in the conjunctiva of normal and, in an increased number, in inflamed eyes. These cells were uniformly CD11b+, CD3-, and Gr-1-, suggesting a monocytic origin, similar to the VEGFR-3+ cells in the cornea. Nearly half of the VEGFR-3+ cells were also positive for MHC class II expression, and none were positive for CD80 (B7-1), indicating their relative immature status. In contrast to the recently described VEGFR3+ corneal cells, however, VEGFR-3+ conjunctival cells did not express the DC marker CD11c. We conclude that in addition to its known role in lymphangiogenesis, VEGFR-3 is also expressed by a conjunctival monocyte/macrophage lineage, implicating a potential relationship between lymphangiogenesis and leukocyte trafficking in the ocular surface.

Animals↗
PubMed2004

Tear film and ocular surface tests in animal models of dry eye: uses and limitations.

Many ocular surface tests have been developed for the clinical diagnosis of keratoconjunctivitis sicca, and several have been used to 'validate' animal models of Sjogren's and non-Sjogren's dry eye. However, many of these tests themselves have not been systematically studied or standardized, and yet their use in animal models of dry eye is common. This review provides a rational approach and systematic review of the tear film and ocular surface tests described in the literature that may be applicable to the current animal models of dry eye, with particular emphasis on their limitations, along with some suggestions regarding their standardization and applications in eye research.

Animals↗
PubMed2004

Ex vivo adenovirus-mediated gene transfer to corneal graft endothelial cells in mice.

PURPOSE: Genetic modulation of donor tissue before corneal transplantation may have the potential to modulate alloimmunity and/or to prevent corneal endothelial cell death. This study was conducted to optimize adenovirus-mediated gene transfer to donor corneal endothelium and to delineate the kinetics of marker gene expression in syngeneic and allogeneic corneal grafts. METHODS: BALB/c mouse corneas were incubated with replication-deficient adenovirus encoding green fluorescent protein (GFP) or empty vector ex vivo at a dose of 6 x 10(7) or 6 x 10(6) PFU at temperatures of 4 degrees C or 37 degrees C. After ex vivo infection, the donor corneas were transplanted orthotopically to BALB/c or C57BL/6 recipients. After transplantation, localization of GFP in the grafts was determined in cryosections of enucleated eyes, and GFP expression in the grafts was visualized in vivo by using epifluorescence microscopy over 12 weeks. All grafts were evaluated clinically by slit lamp biomicroscopy. RESULTS: GFP expression was found to be restricted to the corneal endothelium. In vivo expression of GFP in syngeneic corneal grafts was demonstrated for up to 12 weeks. Syngeneic grafts incubated with the vector at 4 degrees C exhibited a more extensive and longer duration of expression of green fluorescence than grafts incubated at 37 degrees C. Moreover, the syngeneic grafts infected at 4 degrees C maintained their transparency, whereas those infected at 37 degrees C displayed a high degree of opacity. Corneal allogeneic grafts infected with a low dose of the vector displayed longer GFP expression and graft survival than the allogeneic grafts infected with a high dose of the viral vector. CONCLUSIONS: Adenoviral vector can selectively and efficiently deliver exogenous gene(s) to the endothelium of corneal grafts during hypothermic organ preservation. Gene expression is retained in vivo in corneal syngeneic grafts for longer periods than are allogeneic grafts.

Adenoviridae↗