Circumpapillary ganglion cell complex thickness to diagnose glaucoma: A pilot study.

PURPOSE: The purpose of this study is to evaluate the applicability of a new optical coherence tomography parameter, the circumpapillary ganglion cell complex (cpGCC) thickness for glaucoma diagnostics. SUBJECTS AND METHODS: The RS-3000 Advance SD-OCT (NIDEK, Aichi, Japan) was used to measure global and sector macular GCC (mGCC) thickness, circumpapillary retinal nerve fiber layer (cpRNFL) thickness, cpGCC, and circumpapillary total retina (cpTR) thickness in 1 eye of 48 preperimetric/early perimetric primary open-angle glaucoma patients and 28 healthy Japanese participants. Area under the receiver-operating characteristic (AUROC) curves were used for between-method comparisons. RESULTS: All global and sector parameters except for the nasal sector differed significantly between the patient groups (P ≤ 0.009). The AUROC for global mGCC (0.917) was significantly higher (P < 0.01) than that for global cpRNFL (0.760), global cpGCC (0.828), and global cpTR (0.812). The AUROC values of global and temporal cpGCC were significantly higher than those of the corresponding cpRNFL parameters (P < 0.05). Correlation between the visual field means deviation and each of the global thickness parameters was similar (r: 0.418-0.473, P< 0.001). At >90% specificity, the cpGCC, cpTR, and cpRNFL were able to detect 4%, 10%, and 0% of glaucoma eyes that were not detected by the mGCC thickness. CONCLUSIONS: In Japanese eyes, the diagnostic accuracy of cpGCC is lower than that of mGCC but higher than that of cpRNFL. Our results suggest that the use of cpGCC may not improve glaucoma diagnostics when there is no macular disease but may be of benefit when macular diseases prevent successful mGCC measurements.

Differences of Intrasession Reproducibility of Circumpapillary Total Retinal Thickness and Circumpapillary Retinal Nerve Fiber Layer Thickness Measurements Made with the RS-3000 Optical Coherence Tomograph.

PURPOSE: To evaluate the intrasession reproducibility of various thickness parameters used to diagnose and follow-up glaucoma, in particular circumpapillary total retinal thickness (cpTR) provided by the RS-3000 optical coherence tomograph (OCT). METHODS: Fifty-three healthy eyes of 28 subjects underwent three consecutive imaging with the RS-3000 Advance OCT (NIDEK, Aichi,Japan) to evaluate the intrasession reproducibility of circumpapillary total retinal thickness (cpTR), circumpapillary retinal nerve fiber layer thickness (cpRNFL), macular ganglion cell complex thickness (mGCC) and macular total retina thickness (mTR) measurements. Intraclass correlation (ICC), coefficient of variation (CV) and reproducibility coefficient (RC) were calculated for each parameter. RESULTS: The ICC and CV values for mean cpTR and cpRNFL were 0.987 and 0.897, and 0.60% and 2.81%, respectively. The RC values for the mean cpTR and cpRNFL were 5.95 µm and 9.04 µm, respectively. For all cpTR parameters the ICC values were higher and both the CV and RC values were lower than those for the corresponding cpRNFL parameters. The ICC and CV values for superior mGCC, inferior mGCC, superior mTR and inferior mTR were 0.983, 0.980, 0.983 and 0.988, and 0.84%, 0.98%, 0.48% and 0.43%, respectively. The RC values for superior mGCC, inferior mGCC, superior mTR and inferior mTR were 2.86 µm, 3.12 µm, 4.41 µm and 4.43 µm, respectively. CONCLUSIONS: Intrasession reproducibility of cpTR, mGCC and mTR measurements made on healthy eyes was high. Repeatability of cpTR measurements was better than that of the corresponding cpRNFL measurements. These results suggest that future clinical investigations addressing detection of glaucoma and glaucomatous progression with the RS-3000 OCT may benefit from focusing on the cpTR parameters.

Clodronate stimulates bone formation as well as inhibits bone resorption and increases bone mineral density in rats fed a low-calcium diet.

The pharmacological actions of bisphosphonates are due to the inhibitory effects on bone resorption, but little is known about the bisphosphonate action on bone formation. The purpose of this study is to elucidate the actions of bisphosphonates, clodronate, on bone formation in the experimental in vivo and in vitro rat models. The bone mineral density (BMD) was decreased in the rats fed a low-calcium diet (0.05% Ca) for 6 days compared with the rats fed a normal-calcium diet (0.5% Ca). The decrease in BMD was suppressed in the 2 mgP/day and the 4 mgP/day clodronate administrations. Bone formation rate (BFR) in rats fed a low-calcium diet was significantly increased compared with the rats fed a normal-calcium diet, and the 2 mgP clodronate administration further increased the BFR. In the cultured rat bone marrow cells, the area of mineralized nodules was significantly increased at 10(-7) and 10(-6) M clodronate, but high concentration of clodronate decreased the area. From these results, it is concluded that clodronate stimulates bone formation when the drug was given to a rat with a relatively lower dose that is sufficient to prevent bone resorption and that this effect may be due to the stimulatory effect on the differentiation process of osteoblasts.

Role of serine 249 of ezrin in the regulation of sodium-dependent phosphate transporter NaPi-IIa activity in renal proximal tubular cells.

Type IIa sodium-dependent phosphate transporter (NaPi-IIa) is responsible for renal phosphate reabsorption and maintenance of systemic phosphate homeostasis in mammals. Macromolecular complex formation of NaPi-IIa with sodium-proton exchanger related factor-1 (NHERF-1) and ezrin is important for apical membrane localization in the proximal tubular cells. Here, we investigated the interactions of the ezrin phosphomimetic mutation of serine to aspartic acid at 249 with NHERF-1 and the inhibition of apical membrane localization of NaPi-IIa. In vitro phosphorylation analysis revealed that serine 249 of human ezrin serves as a phosphorylation site for protein kinase A. The N-terminal half of ezrin had a dominant negative effect on the phosphate transport activity and inhibited the apical localization of NaPi-IIa in renal proximal tubular cells. We found that the phosphomimetic S249D mutant interfered with the inhibitory effects of the dominant negative mutant on the transport and localization of NaPi-IIa. The S249D mutant also inhibited the interaction with NHERF-1. Therefore, serine 249 of ezrin can play important roles in the regulation of the complex formation and membrane localization of NaPi-IIa.

Analysis of different complexes of type IIa sodium-dependent phosphate transporter in rat renal cortex using blue-native polyacrylamide gel electrophoresis.

Type IIa sodium-dependent phosphate transporter (NaPi-IIa) can be localized in the apical plasma membrane of renal proximal tubule to carry out a rate-limiting step of phosphate reabsorption. For the apical localization, NaPi-IIa is required to form a macromolecular complex with some adaptor proteins such as Na(+)/H(+) exchanger regulatory factor 1 (NHERF-1) and ezrin. However, the detail of macromolecular complex containing NaPi-IIa in the apical membrane of the renal proximal tubular cells has not been clarified. In this study, we identified at least four different complexes (220, 480, 920, 1,100 kDa) containing NaPi-IIa by using blue-native polyacrylamide gel electrophoresis. Interestingly, LC-MS/MS analysis and immunoprecipitation analysis reveal that megalin is a component of larger complexes (920 and 1,100 kDa). In addition, NaPi-IIa can be heterogeneously co-localized with ezrin and megalin on the apical membrane of renal proximal tubuler cells by fluorescence microscopy analysis. These results suggest that NaPi-IIa can form some different complexes on the apical plasma membrane of renal proximal tubular cells.