Biomedical subjects

John Choi

Publications and source records attributed to John Choi.

6 recordsLinked to original sources

PubMed2006

Mooren ulcer: an immunopathologic study.

PURPOSE: To determine the pattern and distribution of mononuclear cells, adhesion, and co-stimulatory molecules in the conjunctiva of patients with Mooren ulcer. METHODS: Conjunctival biopsy specimens were obtained from 6 patients with Mooren ulcer and 6 healthy individuals. Immunohistochemistry was performed on frozen sections of the cryopreserved human conjunctivas using monoclonal antibodies directed against CD1alpha, CD3, CD4, CD8, CD20, CD25, CD57, and CD68 cells; the adhesion molecules E-selectin, vascular cell adhesion molecule-1 (VCAM-1), very late activation-4 (VLA-4), ICAM-1, and LFA-1; and the co-stimulatory molecules CD28, B7-1, B7-2, and CTLA-4. RESULTS: Differences in expression on the conjunctival epithelium from patients with Mooren ulcer and normal subjects were noted only for VCAM-1, VLA-4, ICAM-1, and LFA-1. The ratio of CD4+/CD8+ cells in Mooren ulcer specimens was significantly higher (3.5-fold). However, in the substantia propria, Mooren ulcer specimens revealed significantly increased numbers of CD1alpha+, CD3+, CD4+, CD20+, CD28+, B7-1+, B7-2+, and CD68+ cells. The ratios of CD4+/CD8+ cells and B7-2+/antigen-presenting cells in Mooren ulcer specimens were significantly higher (5-fold). All tested adhesion molecules showed significant up-regulation in the patients' conjunctivas. Mooren ulcer vascular endothelial cells prominently expressed E-selectin, VCAM-1, VLA-4, and ICAM-1 compared with normal conjunctiva. CONCLUSION: The simultaneous presence of multiple types of inflammatory cells, adhesion, and co-stimulatory molecules in Mooren ulcer conjunctiva suggests that their interaction may contribute to a sustained immune activation as at least part of the pathogenic mechanism of this disorder.

Antibodies, Monoclonal↗

PubMed2005

Ahmed valve implantation for uncontrolled pediatric uveitic glaucoma.

PURPOSE: We sought to evaluate the safety and efficacy of Ahmed valve implantation for the management of glaucoma associated with chronic uveitis in pediatric patients. METHODS: A retrospective chart review was conducted of 6 pediatric patients (7 eyes) who underwent Ahmed valve implantation because of refractory uveitic glaucoma. Intraocular pressure (IOP) reduction, preoperative and postoperative visual acuities, the number of hypotensive medications required, and complications associated with the operation were evaluated. RESULTS: Mean follow-up was 36.8 months (range, 6-60). At the last visit, all 7 eyes had IOPs between 9 and 18 mm Hg (average, 12.1). IOP reduction averaged 69.6% (P = 0.0005, paired t-test). The number of hypotensive agents was reduced from an average of 3 to an average of 0.71 medicines per eye (P = 0.001). The only complication was hemorrhagic choroidal detachment postoperatively in two eyes; both resolved within one month. CONCLUSIONS: For children with good immunomodulatory control of their inflammation and appropriate follow-up, Ahmed valve implantation can be an effective and safe procedure for treating pediatric uveitic glaucoma.

Adolescent↗

PubMed2005

Ocular compensation for alternating myopic and hyperopic defocus.

During development, the eye grows under visual feedback control, as shown by its compensating for defocus imposed by spectacle lenses. Under normal conditions the sign and magnitude of defocus vary with viewing distance, accommodative status and other factors. To explore how periods of myopic and hyperopic defocus are integrated over time we presented rapidly alternating episodes of myopic and hyperopic defocus by sequentially illuminating a nearby scrim and the wall beyond it to chick eyes wearing lenses that put the far point between the two surfaces. We found that equal periods of myopic and hyperopic defocus generally led to compensatory hyperopia, showing that myopic defocus had a disproportionate effect. Furthermore, the degree of hyperopia depended on the frequency of alternation: low frequencies (1 cycle/30 min) resulted in more hyperopia, whereas at high frequencies (1 cycle/s) the myopic and hyperopic defocus nearly cancelled each other. If similar temporal integration effects apply to humans, they may help explain why brief accommodation events may not influence lens-compensation and why a child's total reading time may be a poor predictor of myopic progression.

Accommodation, Ocular↗

PubMed2005

Reconstitution of trabecular meshwork GAGs: influence of hyaluronic acid and chondroitin sulfate on flow rates.

PURPOSE: This study was undertaken to determine whether the concentration of hyaluronic acid (HA) and of chondroitin sulfate (CS) occurring in the normal and the primary open-angle glaucoma (POAG) trabecular meshwork (TM) influences flow rates in vitro as a function of pressure. METHODS: We tested 100, 500, and 4000 kDa molecular weight HA, CS, reconstituted normal and POAG TM HA-CS and juxtacanalicular connective tissue (JCT) HA-CS in a micro test chamber to determine initial and steady-state flow rates. The resistance and permeability (Ko) were calculated; Linear Newtonian mechanics were used to determine the possible contributions of the hydrophobic interactions of HA. RESULTS: Initial flow rates increased in the pressure range of 5 to 20 mm Hg for the three HA preparations and the flow rates declined in the pressure range of 20 to 40 mm Hg. Flow rates of reconstituted normal TM and JCT were optimum at 10 mm Hg and then declined with increasing pressure. Flow rates of reconstituted POAG TM and JCT were optimum only at 5 mm Hg and then declined. The steady-state rate of POAG JCT HA-CS at 10 mm Hg was slow: the transition time (ie, the time required to start an increase in flow rate) was 29 hours and the lag time (ie, the time required to obtain steady-state flow rate) was 17 hours. The maximum flow rate in POAG JCT HA-CS decreased by 37.2% from the normal JCT HA-CS. The calculated resistance of reconstituted POAG JCT HA-CS was approximately 18% of the total resistance of the human JCT compared with 10% in the normal JCT. CONCLUSIONS: Hyaluronic acid and CS contribute to flow resistance and influence flow rate in vitro. The influence of HA is particularly sensitive to an increase in the pressure gradient, which may be caused by unfolding of the hydrophobic interactions of HA polymers that further entangles the HA polymer. The POAG JCT HA-CS concentrations represent a significant factor in outflow resistance in POAG, particularly at higher pressures.

Animals↗

PubMed2005

Soluble CD44 is cytotoxic to trabecular meshwork and retinal ganglion cells in vitro.

PURPOSE: Current glaucoma research targets neuroprotective therapies for retinal ganglion cells (RGCs) in primary open-angle glaucoma (POAG). The purpose of this study was to determine whether the 32-kDa ectodomain fragment of CD44-soluble CD44 (sCD44)-which is increased in the aqueous of patients with POAG, affects RGC and trabecular meshwork (TM) cell survival in vitro. METHODS: sCD44 was isolated from human or fetal calf serum (FCS) by urea solubilization and immunoprecipitation. A transformed rat RGC-like cell line (RGC-5), human and bovine TM cells, and control cells were grown in Dulbecco's modified Eagle's medium containing 10% FCS until confluent and then were incubated in medium containing 0.1% FCS and treated with various doses of purified sCD44 and 17-alpha-methyl testosterone (17-alpha-MT). The cytotoxicity of sCD44 was verified by heat-inactivation, pretreatment with a pan-caspase inhibitor, and coadministration of anti-CD44 neutralizing antibody or hyaluronic acid (HA). Cell viability was assessed by trypan blue staining, cell counting, and phase-contrast microscopy. RESULTS: There was a statistically significant dose- and time-dependent decrease in the number of cells and viability in the RGC-5 and TM cells treated with sCD44. Within 12 hours of sCD44 treatment, RGC-5 and TM cells displayed cell rounding, detachment, and swelling. sCD44-induced cell death was cell specific. Smooth muscle cells were resistant to sCD44, whereas human cortical neuronal-like cells were susceptible to sCD44 after 24 hours, but recovered. The cytotoxicity of sCD44 was blocked by heat-inactivation, pretreatment with a pan-caspase inhibitor, or coadministration of anti-CD44 antibody or HA. 17-alpha-MT prevented sCD44 cytotoxicity in both RGC-5 and TM cells. CONCLUSIONS: The results indicate that exogenous sCD44 adversely affects RGC-5 and TM cell survival in vitro by activating proapoptotic pathways.

Animals↗

PubMed2005

Hypophosphorylation of aqueous humor sCD44 and primary open-angle glaucoma.

PURPOSE: The ectodomain of CD44, the principal receptor for hyaluronic acid (HA), is shed as a 32-kDa fragment-soluble CD44 (sCD44)-which is cytotoxic to trabecular meshwork (TM) cells and retinal ganglion cells (RGCs) in culture. The purpose of this study was to characterize sCD44 further by determining the phosphorylation of aqueous humor sCD44 in normal and primary open-angle glaucoma (POAG). METHODS: Aqueous humor samples of patients were subjected to CD44 enzyme-linked immunosorbent assay (ELISA) and two-dimensional (2-D) polyacrylamide gel electrophoresis, followed by Western blot analysis with anti-CD44, anti-serine/threonine, and anti-tyrosine phosphospecific antibodies, to determine sCD44 concentration, isoelectric point (pI), and phosphorylation, respectively. The bioactivity of hypophosphorylated sCD44 was tested in cell culture and HA affinity columns. RESULTS: Two-dimensional Western blot analysis revealed that the representative pI of the 32-kDa sCD44 was 6.96 +/- 0.07 in POAG versus 6.38 +/- 0.08 in normal (P < 0.0004). Enzymatic dephosphorylation of sCD44 resulted in a basic shift in the pI. The normal aqueous humor sCD44 was positive for serine-threonine phosphorylation; however, POAG sCD44 was hypophosphorylated. Hypophosphorylated sCD44 was more toxic to TM and RGC cells than standard sCD44, and hypophosphorylated sCD44 had decreased affinity to HA, particularly with increased pressure. CONCLUSIONS: POAG aqueous is characterized by posttranslational change in the pI of sCD44 and hypophosphorylation, which clearly distinguished POAG from normal aqueous humor. The high toxicity and low HA-binding affinity of hypophosphorylated sCD44 may represent specific pathophysiologic features of the POAG disease process.

Aqueous Humor↗