PubMed Health⌕ Search

Biomedical subjects

H S Dua

Publications and source records attributed to H S Dua.

At least 19 recordsLinked to original sources
PubMed1997

Phenotypic analysis of resident lymphoid cells in the conjunctiva and adnexal tissues of rat.

The conjunctival associated lymphoid tissue is considered to be an integral part of the mucosal immune system. Under normal circumstances immune mechanisms in mucosal associated lymphoid tissue of the gut and bronchus can selectively suppress, rather than enhance, immune responsiveness to encountered antigens, inducing a state of tolerance. It is possible that conjunctival associated lymphoid tissue can also induce a state of tolerance to encountered antigens. Such a response may be exploited to modulate immune mediated ocular disease. Enhanced tolerance may protect the host against foreign antigen. Alternatively, under certain circumstances when the normal immune system is altered or disrupted the mucosal tissue may act to induce sensitisation and trigger immune mediated disease. The rat is frequently used as an animal model of immune mediated eye disease, but the normal profile of immune cells in the rat conjunctiva has not been studied. This information is essential for meaningful interpretation in the experimental situation. In this study we examined the immunophenotype of lymphoid tissue associated with the conjunctiva, lacrimal gland and Harderian gland of the Lewis rat. CD4+, Ia+ and the monocyte/macrophage population of cells were found predominantly in the substantia propria of the conjuctiva and interstitial connective tissue of the glands. CD8+ cells were distributed mainly in relation to the conjunctival and glandular epithelium. Goblet cells stained strongly with the monoclonal antibody (MAb) MRC OX-39, which is a marker for IL-2 receptors. The overall pattern of distribution of immunocompetent cells in the rat was found to be similar to that reported in humans.

Animals↗
PubMed1997

E-cadherin distribution and epithelial basement membrane characteristics of the normal human conjunctiva and cornea.

The conjunctival mucosa has several similarities to the mucosal immune system of the gut and bronchus. Like the gut and bronchial mucosa, the conjunctiva is capable of inducing tolerance to encountered antigens and possesses a repertoire of CD8+ intraepithelial lymphocytes (IELs) bearing the human mucosal lymphocyte-1 antigen (HML-1) which has been shown to be an alpha E beta 7 integrin. The epithelial cells surface ligand for HML-1 is E-cadherin. The distribution of E-cadherin in the normal human conjunctiva and cornea is not known. We investigated E-cadherin distribution in the conjunctiva and cornea by immunohistochemistry. E-cadherin was found to be present in all layers of the conjunctival epithelium but not in corneal epithelium. In the conjunctiva it may act as a ligand for the HML-1+ IELs. The specific location of IELs along the basal cells of the conjunctiva compared with the generalised distribution of E-cadherin through all layers, indicates that factors other than E-cadherin binding determine the distribution of HML-1+ IELs. We performed electron microscopy on de-epithelialised conjunctival and corneal samples. We demonstrated the presence of epithelial basement membrane pores in the conjunctiva but not in the cornea. Lymphocyte migration from the substantia propria to the intraepithelial compartment appears to occur through these pores, which may also serve as a conduit for antigen presentation by epithelial antigen presenting cells (APCs) to lymphocytes in the substantia propria.

Aged↗
PubMed1996

The effect of topical cyclosporin on conjunctiva-associated lymphoid tissue (CALT).

Topical cyclosporin A is increasingly being used in the treatment of ocular surface immune-mediated disorders. The availability of the drug in oil-based vehicles or collagen shields has restricted its use because of ocular irritation or blurring of vision. Although topical cyclosporin is being used more frequently, its effect on the immunocompetent cells of the conjunctiva is not known. Our aim was to study the effect of cyclosporin instillation on the immunocomponent cells of conjunctiva-associated lymphoid tissue (CALT) of Lewis rat, using a novel method of topical drug delivery. A suspension of collagen bits impregnated with cyclosporin A was instilled into eyes of Lewis rats for 4 days (group 1) or 8 days (group 2). Control rats (group 3) received the suspension without cyclosporin. Frozen sections of eyelids and conjunctiva were immunostained with the following monoclonal antibody markers: W3/13 (CD3), W3/25 (CD4, macrophages), OX-8 (CD8), MARD-3 (B cells), ED1, ED2 (macro/monocytes), OX-6 (class II MHC, Ia) and OX-39 (CD25, IL-2 receptor). Intraepithelial (IE) and substantia propria cells for each subset were counted and expressed as numbers per section. By day 8, intraepithelial and substantia propria cells for all the above markers, except B cells, showed a significant reduction in numbers. The p values were < 0.02 for W3/13 (CD3), W3/25 (CD4), OX-8 (CD8), OX-39 (CD25) (IE only), ED1, ED2 and OX-6 positive cells. Goblet cells of control animals showed strong positive reaction with OX-39 (CD25) antibody. This was completely abolished following 8 days of topical cyclosporin. This study demonstrated that topical cyclosporin A induces a marked reduction in numbers of all subtypes of immunocompetent cells in the conjunctival epithelium and substantia propria.

Administration, Topical↗
PubMed1996

Vortex or whorl formation of cultured human corneal epithelial cells induced by magnetic fields.

The terms 'vortex keratopathy' and 'hurricane keratopathy' describe two similar conditions affecting the corneal surface. In the former, a vortex or whorl pattern is seen on the corneal surface and is due to the deposition of substances such as pigment, iron or drugs in the epithelial cells. In the latter, a similar pattern is presented by migrating epithelial cells but, unlike the former, the pattern is rendered more visible by fluorescein staining. Both represent the migratory pattern of normal epithelial cells which is otherwise not visible due to the slow rate of epithelial turnover and migration. The whorl pattern has a clockwise predisposition in the majority of cases and is hypothesised to be due to the influence of ocular electro-magnetic fields on the migrating epithelial cells. In this study we tested in vitro the effect of static magnetic fields on corneal epithelial cells. We were able to reproduce dramatic vortex or whorl patterns in response to magnetic fields, but without preferential migration towards the North or South Pole.

Adult↗
PubMed1995

The ocular surface as part of the mucosal immune system: conjunctival mucosa-specific lymphocytes in ocular surface pathology.

The mucosal immune system includes mucus membranes of the gut, respiratory and urogenital tracts. Mucosa-specific, intraepithelial lymphocytes (IELs), that correspond to the suppressor/cytotoxic subset and also express the human mucosal lymphocyte antigen (HML-1), are a unique component of this system. We have recently demonstrated these cells in the human conjunctiva, establishing the ocular surface as an integral part of the mucosal immune system. In this study we examined the distribution of lymphocyte subsets, with particular attention to mucosa-specific lymphocytes, in two ocular surface disorders, namely conjunctival intraepithelial neoplasia (CIN) and ocular cicatricial pemphigoid (OCP). Cryosections of biopsy specimen were immunostained using a panel of monoclonal antibodies against different lymphocyte subsets. In CIN, the CD8/HML ratio was decreased (1 +/- 0) and CD8/CD4 ratio was reversed (0.54 +/- 0.21). HML-1+ cells were distributed throughout the epithelial layers of dysplastic tissue. Biopsy specimens of OCP showed normal ratios of CD8/HML (1.4 +/- 0.16) but the CD8/CD4 was low (1.29 +/- 0.88). Association of HML-1+ cells with the basal layer of normal epithelium and with all layers of dysplastic epithelium suggests that expression of HML-1 antigen may be induced by actively dividing cells. HML-1+ cells may have a role in immune mechanisms associated with ocular surface disorders.

Adult↗
PubMed1995

Positive donor rim culture in penetrating keratoplasty.

A 3-year retrospective study on the risk factors of positive donor rim cultures in penetrating keratoplasty was performed. One thousand and ninety-seven consecutive donor rim cultures were reviewed from the period between June 1990 and October 1993 to determine the rate of culture positivity. The sex, age, diabetes status, use of respirator at time of death, cause of death, harvesting technique, storage time, and corneal storage medium utilized for the donors with positive donor rim culture were compared to those for 100 randomly selected culture negative donor controls. Logistic analysis was performed to eliminate confounding effects. Forty-six of the 1,097 (4.19%) donor rim cultures were positive. We found an association between the in situ technique for donor harvesting and culture negativity (p = 0.03). None of the other donor characteristics was associated with culture positivity. None of the 46 recipients who received the positive culture corneas developed endophthalmitis. In situ cornea harvesting promotes less contamination than enucleation and enriched gentamicin and streptomycin storage medium may further decrease donor rim culture positivity.

Anti-Bacterial Agents↗
PubMed1994

Saps and tears.

Explore the source record for details and available documents.

Animals↗
PubMed1994

Mucosa specific lymphocytes in the human conjunctiva, corneoscleral limbus and lacrimal gland.

Conjunctiva associated lymphoid tissue shows several similarities to mucosa associated lymphoid tissue of the gut and respiratory tract. These similarities have been described in relation to lymphocyte subpopulations and epithelial cell morphology. However, unlike the lymphoid tissue of the gut and respiratory tract, mucosa specific lymphocytes have not been described in the ocular mucosa. In this study we demonstrated the presence of mucosa specific lymphocytes bearing the Human Mucosal Lymphocyte-1 antigen (beta 7 integrin), in the human conjunctiva, limbus and lacrimal gland. The distribution of this subset of lymphocytes corresponded to the distribution of CD8+ T-cells and was found maximally in the epithelium of the epibulbar conjunctiva and in the lacrimal gland. The Human mucosal lymphocyte antigen may function to determine mucosal homing of this particular subset of CD8+ T-cells, which in turn, may have special function in immunological defense and tolerance mechanisms occurring at mucosal surfaces.

Adolescent↗
PubMed1993

Corneal epithelial cell migration in humans: 'hurricane and blizzard keratopathy'.

Replicative turnover of the corneal epithelium is believed to occur from a population of stem cells located at the corneo-scleral limbus. During the healing of corneal epithelial wounds, sheets of epithelial cells move centripetally from the limbus and circumferentially along the limbus to cover the defect. A whorled or vortex pattern, similar to that seen in cornea verticillata, has been reported to occur on the corneal surface as an effect of topical steroid medication, during the healing of grafted corneas. This condition has been termed 'hurricane keratopathy'. We have noted this appearance in 6 patients who did not have corneal grafts. In all our patients the whorled pattern was best visible on fluorescein staining. This feature differentiates 'hurricane keratopathy' from cornea verticillata secondary to deposition of substances in corneal epithelial cells. Further, in all our patients the vortex was clockwise. Examination of illustrations of 'hurricane keratopathy' and cornea verticillata reported in the literature reveals that the whorled pattern is almost always clockwise. We believe that this specific pattern is likely to be due to the effect of the electromagnetic fields of the eye on the migrating epithelial cells and present a theory to explain this phenomenon. In 3 eyes of 2 other patients with chronic epitheliopathies we observed a random distribution of cells that did not conform to any specific pattern. We have termed this condition 'blizzard keratopathy'.

Adult↗
PubMed1993

A spectrum of clinical signs in anterior uveitis.

The range of clinical changes that occur in posterior uveitis have been well documented. We describe two clinical features of anterior uveitis which we have termed 'iris pigment epithelitis' and 'iris vasculitis'. Other clinical forms of iritis also exist and together with our described findings parallel the spectrum of clinical presentations in posterior uveitis.

Adult↗
PubMed1993

Ultrastructural pathology of experimental autoimmune uveitis in the rat.

Experimental autoimmune uveoretinitis (EAU) has been extensively studied as a model for human posterior uveitis, however, few ultrastructural studies of EAU in the rat have been reported. In the present report we document a systematic time-course study of the posterior segment changes in the Lewis rat. The disease varied somewhat in severity in animals sacrificed at identical times after immunisation. In the prodromal stage of the disease, usually around day 14, early pathological changes included mild peripapillary vasculitis and low grade mononuclear and neutrophilic infiltration of the subretinal space with phagocytosis of the rod outer segments. The features of the severe or active diseases were most evident on day 21 and included mixed cellular infiltrate of the vitreous, subretinal serohaemorrhagic exudate, focal retinal detachment and necrosis. Outer retinal destruction was often most severe adjacent areas of retinal vasculitis. Focal monocytic subpigment epithelial microgranulomas, reminiscent of Dalen-Fuch's nodules in humans, were also identified. By day 28 and 49 active inflammation had subsided and large segments of the outer retina were completely destroyed. The retinal pigment epithelium (RPE) also showed signs of activation in the vicinity of focal retinochoroidal mononuclear infiltrates including multilayering, proliferation and increased phagocytosis. Finally, neovascularisation of the RPE by non-fenestrated capillaries derived from the retinal vasculature was evident in the late stages of the disease.

Acute Disease↗
PubMed1992

Inhibition of experimental autoimmune uveitis by retinal photoreceptor antigens coupled to spleen cells.

Experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) are CD4+ T cell-mediated inflammatory diseases of the uveal tract and retina of the eye and of the pineal gland. EAU and EAP can be induced by several retinal autoantigens including S-antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP). In this study we investigated the effect of intravenous administration of S-Ag and IRBP coupled to syngeneic spleen cells on the development of EAU and EAP. Injection of S-Ag or IRBP coupled to spleen cells 5 days prior to immunization with native S-Ag or IRBP, respectively, was effective in preventing the induction of EAU and EAP in LEW rats. Conversely, LEW rats receiving S-Ag-coupled spleen cells and challenged with IRBP or LEW rats receiving IRBP-coupled spleen cells and challenged with S-Ag developed a severe EAU within 10 days to 2 weeks following immunization, as did all control animals receiving sham-coupled spleen cells and challenged with the two retinal antigens. The results show that the administration of retinal autoantigens coupled to spleen cells effectively protects against the development of EAU when animals are subsequently challenged with the tolerizing antigen but not when challenged with another unrelated pathogenic retinal autoantigen.

Animals↗