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Biomedical subjects

Anshoo Choudhary

Publications and source records attributed to Anshoo Choudhary.

5 recordsLinked to original sources
PubMed2006

Herpes simplex keratitis.

Herpes simplex keratitis (HSK) results from an infection with the herpes simplex virus type 1 (HSV-1) also known as human herpesvirus type 1 (HHV-1). Primary infection may involve an ocular or non-ocular site, following which latency might be established principally in the trigeminal ganglion but also in the cornea. During latency, the virus appears as a circular episome associated with histones with active transcription only from the region encoding the latency-associated transcript (LAT). The LAT region is implicated in neuronal survival, anti-apoptosis, virulence, suppression of transcription, establishment of and reactivation from latency. The initial keratitis may develop after infection through the "front door route" (entry into the ocular surface from droplet spread) or "back door route" (spread to the eye from a non-ocular site, principally the mouth). The initial ocular infection may be mild. Visual morbidity results from recurrent keratitis, which leads to corneal scarring, thinning and neovascularisation. Although, recurrent disease may potentially occur through anterograde axonal spread from the trigeminal ganglion to the cornea, recent evidence suggests that HSV-1 in the cornea may be another source of recurrent disease. The pathogenesis and severity of HSK is largely determined by an interaction between viral genes encoded by the strain of HSV-1 and the make up of the host's immune system. Herpetic stromal disease is due to the immune response to virus within the cornea and the ability of the strain to cause corneal stromal disease is correlated with its ability to induce corneal vascularisation. The pathogenesis of corneal scarring and vascularisation is uncertain but appears to be a complex interaction of various cytokines, chemokines and growth factors either brought in by inflammatory cells or produced locally in response to HSV-1 infection. Evidence now suggests that HSV-1 infection disrupts the normal equilibrium between angiogenic and anti-angiogenic stimuli leading to vascularisation. Thrombospondin 1 and 2, matricellular proteins, involved in wound healing are potent anti-angiogenic factors and appear to be one of the key players. Elucidating their roles in corneal scarring and vascularisation may lead to improved therapies for HSK.

Animals↗
PubMed2006

Mycophenolate mofetil as an immunosuppressive agent in refractory inflammatory eye disease.

PURPOSE: The aim of this study was to assess the role of mycophenolate mofetil (MMF) in refractory inflammatory eye disease. METHODS: Retrospective, noncomparative, interventional case series of all patients commenced on MMF between 1999 and 2005 for refractory inflammatory eye disease at St Paul's Eye Unit (Liverpool, UK). Main outcome measures noted were control of inflammation, steroid-sparing effect, and adverse effects of MMF therapy. RESULTS: Ten (10) patients (2 with sarcoid, 2 with intermediate uveitis, 1 with Vogt-Koyanagi Harada (VKH) syndrome, 1 with ankylosing spondylitis, 1 with juvenile chronic arthritis (JCA), and 3 with scleritis) who were unresponsive or intolerant to previous therapy and/or as a steroid-sparing agent, received 2-3 g of MMF per day for a mean period of 40.5 months (range, 3-67). Nine (9) patients had a favorable response, with diarrhea and insomnia being the main side-effects. MMF had to be withdrawn in 1 patient because of side-effects and in another because of active arthropathy (with stable uveitis). Average number of relapses was reduced from 3.1 per patient per year to 0.8 per patient per year (P < 0.005). A steroid-sparing effect was achieved in all patients. Visual acuity improved in 8 patients. CONCLUSIONS: MMF appears to be a safe and effective second- or third-line adjunct/alternative immunosuppressant in these difficult cases and works well in combination with cyclosporin A, tacrolimus, and antitumor necrosis factor (TNF) agents. It has potential as a firstor second-line agent and can be considered at a dose of 3 g/day in refractory cases.

Adult↗
PubMed2005

Thrombospondin 1, thrombospondin 2 and the eye.

Thrombospondin 1 and thrombospondin 2 (TSP1 and TSP2), which comprise the subgroup A thrombospondins, are matricellular proteins. As matricellular proteins, they modulate interactions between cells and the cellular environment, regulate cell adhesion and typically are expressed during tissue formative processes. In general, TSP1 and TSP2 counter angiogenesis (including tumour angiogenesis) and play important but contrasting roles during cutaneous repair. The two proteins are involved in development, including that of the eye, although evidence suggests that they have their greatest impact during tissue production in the adult. In the normal adult eye, they tend to be found at sites of ongoing matrix synthesis or cell-matrix interactions. At these sites, the two proteins possibly influence cellular differentiation and/or basement membrane deposition. TSP1 is also present in the intraocular fluids and drainage pathway, where it may function in maintaining the anti-angiogenic environment and in intraocular pressure control, respectively. TSP1 could also be involved in ocular immune privilege. Unlike in skin wounds, where TSP1 is derived from the blood and is present only in the early phases of repair, ocular tissue damage appears to lead to protacted TSP1 synthesis by local cells. This response might help suppress angiogenesis in the transparent tissues of the eye and so lessen visual axis opacification following injury. However, TSP2, which is also produced by damaged ophthalmic tissue and may be especially important in matrix organisation, seems to augment contraction in anomalous intraocular fibrosis. Elucidating the roles of TSP1 and TSP2 in ocular physiology and pathobiology may lead to improved therapies for neovascular, neoplastic, reparative and other ophthalmic diseases.

Animals↗
PubMed2005

Suppression of thrombospondin 1 and 2 production by herpes simplex virus 1 infection in cultured keratocytes.

PURPOSE: Stromal vascularization is a frequent occurrence in herpes simplex keratitis (HSK) and carries a poor prognosis for penetrating keratoplasty. The pathogenesis may involve disruption of the normal equilibrium between angiogenic and anti-angiogenic factors in and around the cornea. Thrombospondin (TSP) 1 and 2 are multifunctional matricellular glycoproteins with potent anti-angiogenic properties and are expressed by human keratocytes in a stromal wound repair model. We hypothesize that the synthesis of these anti-angiogenic proteins by keratocytes is inhibited by HSV1 and that such a mechanism may contribute to stromal vascularization in HSK. METHODS: Nonconfluent monolayers of human keratocytes were infected with HSV1 at a multiplicity of infection of 5 virus particles/keratocyte. Expression of TSP1 and TSP2 was determined by immunohistochemistry and SDS-polyacrylamide gel electrophoresis at 0, 2, 4, 6, 8, 24, 48, and 72 h after infection (ai). Expression of glyceraldehyde 3 phosphate dehydrogenase (GAPDH) served as a control. Expression of immediate early and late viral proteins was also determined. Protein expression was quantified by densitometric analysis of the immunoblot bands. RESULTS: Human keratocytes supported the growth of HSV1 at all times ai. TSP1 and TSP2 were downregulated as early as 4 h ai to a 50% reduction by 8 h (p<0.002), and were absent from 24 h ai (p<0.001). There was no change in the level of expression of GAPDH throughout the duration of the experiment. Immediate early viral proteins (HSV1:ICP27) could be detected from 6 h ai reaching maximum intensity 24 h ai and late proteins (HSV:1gD) were expressed from 24 h. CONCLUSIONS: The synthesis of TSP1 and TSP2 is selectively downregulated by HSV1 infection in human keratocytes. Addition of these proteins or their angio-active peptides in early stage HSK therapy may be an important adjuvant in controlling HSV1 induced corneal vascularization.

Blotting, Western↗