Up-regulation of GABA transporters and GABAA Receptor α1 subunit in tremor rat hippocampus

The loss of GABAergic neurotransmission has been closely linked with epileptogenesis. The modulation of the synaptic activity occurs both via the removal of GABA from the synaptic cleft and by GABA transporters (GATs) and by modulation of GABA receptors. The tremor rat (TRM; tm/tm) is the parent strain of the spontaneously epileptic rat (SER; zi/zi, tm/tm), which exhibits absence-like seizure after 8 weeks of age. However, there are no reports that can elucidate the effects of GATs and GABAA receptors (GABARs) on TRMs. The present study was conducted to detect GATs and GABAR a1 subunit in TRMs hippocampus at mRNA and protein levels. In this study, total synaptosomal GABA content was significantly decreased in TRMs hippocampus compared with control Wistar rats by high performance liquid chromatography (HPLC); mRNA and protein expressions of GAT-1, GAT-3 and GABAR a1 subunit were all significantly increased in TRMs hippocampus by real time PCR and western blot, respectively; GAT-1 and GABAR a1 subunit proteins were localized widely in TRMs and control rats hippocampus including CA1, CA3 and dentate gyrus (DG) regions whereas only a wide distribution of GAT-3 was observed in CA1 region by immunohistochemistry. These data demonstrate that excessive expressions of GAT-1 as well as GAT-3 and GABAR a1 subunit in TRMs hippocampus may provide the potential therapeutic targets for genetic epilepsy.

Screening tests for detecting open-angle glaucoma: systematic review and meta-analysis

PURPOSE: To assess the comparative accuracy of potential screening tests for open angle glaucoma (OAG).

METHODS: Medline, Embase, Biosis (to November 2005), Science Citation Index (to December 2005), and The Cochrane Library (Issue 4, 2005) were searched. Studies assessing candidate screening tests for detecting OAG in persons older than 40 years that reported true and false positives and negatives were included. Meta-analysis was undertaken using the hierarchical summary receiver operating characteristic model.

RESULTS: Forty studies enrolling over 48,000 people reported nine tests. Most tests were reported by only a few studies. Frequency-doubling technology (FDT; C-20-1) was significantly more sensitive than ophthalmoscopy (30, 95% credible interval [CrI] 0-62) and Goldmann applanation tonometry (GAT; 45, 95% CrI 17-68), whereas threshold standard automated perimetry (SAP) and Heidelberg Retinal Tomograph (HRT II) were both more sensitive than GAT (41, 95% CrI 14-64 and 39, 95% CrI 3-64, respectively). GAT was more specific than both FDT C-20-5 (19, 95% CrI 0-53) and threshold SAP (14, 95% CrI 1-37). Judging performance by diagnostic odds ratio, FDT, oculokinetic perimetry, and HRT II are promising tests. Ophthalmoscopy, SAP, retinal photography, and GAT had relatively poor performance as single tests. These findings are based on heterogeneous data of limited quality and as such are associated with considerable uncertainty.

CONCLUSIONS: No test or group of tests was clearly superior for glaucoma screening. Further research is needed to evaluate the comparative accuracy of the most promising tests.

Systematic review of the agreement of tonometers with Goldmann applanation tonometry

OBJECTIVE: To assess the agreement of tonometers available for clinical practice with the Goldmann applanation tonometer (GAT), the most commonly accepted reference device.

DESIGN: A systematic review and meta-analysis of directly comparative studies assessing the agreement of 1 or more tonometers with the reference tonometer (GAT).

PARTICIPANTS: A total of 11 582 participants (15 525 eyes) were included.

METHODS: Summary 95% limits of agreement (LoA) were produced for each comparison.

MAIN OUTCOME MEASURES: Agreement, recordability, and reliability.

RESULTS: A total of 102 studies, including 130 paired comparisons, were included, representing 8 tonometers: dynamic contour tonometer, noncontact tonometer (NCT), ocular response analyzer, Ocuton S, handheld applanation tonometer (HAT), rebound tonometer, transpalpebral tonometer, and Tono-Pen. The agreement (95% limits) seemed to vary across tonometers: 0.2 mmHg (-3.8 to 4.3 mmHg) for the NCT to 2.7 mmHg (-4.1 to 9.6 mmHg) for the Ocuton S. The estimated proportion within 2 mmHg of the GAT ranged from 33% (Ocuton S) to 66% and 59% (NCT and HAT, respectively). Substantial inter- and intraobserver variability were observed for all tonometers.

CONCLUSIONS: The NCT and HAT seem to achieve a measurement closest to the GAT. However, there was substantial variability in measurements both within and between studies.

Influence of corneal structure, corneal responsiveness, and other ocular parameters on tonometric measurement of intraocular pressure.

PURPOSE: To estimate the relationships between ocular parameters and tonometrically measured intraocular pressure (IOP), to determine the influence of ocular parameters on different instrument measurements of IOP, and to evaluate the association of ocular parameters with a parameter called hysteresis. METHODS: Patients presenting at a glaucoma clinic were recruited for this study. Subjects underwent IOP measurement with the Goldmann applanation tonometer (GAT), the TonoPen, and the Reichert Ocular Response Analyzer (ORA), and also measurements of central corneal thickness (CCT), axial length, corneal curvature, corneal astigmatism, central visual acuity, and refractive error. Chart information was reviewed to determine glaucoma treatment history. The ORA instrument provided a measurement called corneal hysteresis. The association between measured IOP and the other ocular characteristics was estimated using generalized estimating equations. RESULTS: Among 230 patients, IOP measurements from the TonoPen read lowest, and ORA read highest, and GAT measurements were closest to the mean IOP of the 3 instruments. In a multiple regression model adjusting for age, sex, race, and other ocular characteristics, a 10 microm increase in CCT was associated with an increase of 0.79 mm Hg measured IOP in untreated eyes (P<0.0001). Of the 3 tonometers, GAT was the least affected by CCT (0.66 mm Hg/10 mum, P<0.0001). Hysteresis was significantly correlated with CCT with a modest correlation coefficient (r=0.20, P<0.0007). CONCLUSIONS: Among parameters related to measured IOP, features in addition to CCT, such as hysteresis and corneal curvature, may also be important. Tonometric instruments seem to be affected differently by various physiologic characteristics.

Determinants of postoperative corneal edema and impact on goldmann intraocular pressure.

PURPOSE: Recent studies report that increased corneal edema because of contact lens wear under closed lids is associated with elevated Goldmann intraocular pressure (GAT IOP). We sought to assess whether the impact of postoperative corneal edema on GAT IOP would be similar and to determine the differential effect of different amounts of edema. METHODS: The setting is a tertiary level cataract clinic in Shantou, China. Pre- and postoperative (day 1) GAT IOP, central corneal thickness (CCT), corneal hysteresis, corneal resistance factor, and radius of corneal curvature were measured for consecutive patients undergoing phacoemulsification surgery by 2 experienced surgeons. Corneal edema was calculated as the percentage increase in CCT. RESULTS: Among 136 subjects (mean age, 62.5 ± 15.4 years; 53.7% women), the mean increase in CCT was 10.3% postoperatively. Greater corneal edema was associated with lower GAT IOP in unadjusted analyses (P < 0.03) and in linear regression models (P < 0.01). In the model, higher corneal resistance factor (P < 0.001), lower corneal hysteresis (P < 0.001), and steeper radius of corneal curvature (P < 0.001) were associated with higher GAT IOP. Among subjects with edema < the median, edema was associated with lower GAT IOP (P = 0.004), whereas among those with edema ≥ the median, edema was not associated with GAT IOP. An increase in CCT of 7% was associated with an 8 mm Hg underestimation of GAT IOP in our models. CONCLUSIONS: The effect of postoperative edema on GAT IOP seems to be the opposite of contact lens-induced edema. The magnitude of the effect is potentially relevant to patient management.