Contribution of nitric oxide-producing cells in normal and diabetic rat retina.

PURPOSE: To examine the immunohistochemical localization of L-arginine and L-citrulline and determine where and how nitric oxide (NO) is produced in the normal and streptozotocin (STZ)-induced diabetic rat retinas. METHODS: NO is produced when L-arginine is changed to L-citrulline by NO synthase (NOS). In normal and STZ-induced diabetic rats, using an immunohistochemical method, we examined the retinal distribution of L-arginine and L-citrulline after intracardiac perfusion. We studied the distribution of NOS after immersed fixation and analyzed the number of neuronal NOS (nNOS)-positive neurons. RESULTS: We observed L-arginine localization in the internal limiting membrane (ILM), the ganglion cell layer (GCL), and the inner nuclear layer (INL). L-Arginine immunoreactivity in the diabetic rat retinas was found in the inner plexiform layer (IPL), as well as in the normal retina. L-Citrulline immunoreactivity in the normal and diabetic retinas was observed in the ILM, the GCL, the IPL, and the INL. nNOS staining in the normal and diabetic rat retinas was observed in the GCL, the IPL and the INL. The number of nNOS-positive amacrine cells was less in the diabetic rat retinas. CONCLUSION: NO might be produced in the GCL and amacrine cells, which show immunoreactivity to L-arginine, L-citrulline, and nNOS. In the early stage of diabetic retinopathy in STZ rat retinas, diabetes disturbed the function of the nNOS-positive amacrine cells and reduced NO production via nNOS.

Switch to latanoprost monotherapy from combined treatment with beta-antagonist and other antiglaucoma agents in patients with glaucoma or ocular hypertension.

PURPOSE: To investigate the effects on intraocular pressure (IOP) and the occurrence of adverse events upon switching directly to latanoprost monotherapy from multiple drug therapy, including a beta-antagonist, for glaucomatous eyes. METHODS: Patients with primary open-angle glaucoma or ocular hypertension and receiving long-term therapy with two or three topical ocular hypotensive drugs (including one topical beta-antagonist) were switched to latanoprost monotherapy for 12 weeks without any intervening washout period. Observations were performed before switching (baseline) and at weeks 4, 8, and 12 after switching to latanoprost monotherapy. RESULTS: Of the 29 enrolled patients, 26 (90%) completed this protocol. Three patients had excessive IOP elevation, and these patients were withdrawn. The switch to latanoprost monotherapy was followed by a significant ( P < 0.0001) mean reduction of 3.9 mmHg at week 12 in per-protocol cases ( n = 26) and a significant ( P = 0.0016) mean reduction of 2.8 mmHg at last postswitch visit in patients in the intent-to-treat analysis group ( n = 29). Adverse ocular events other than IOP elevation were mild. CONCLUSIONS: The switch to latanoprost monotherapy in glaucoma patients receiving multiple drug therapy resulted in an additional, significant IOP reduction.

Symmetry analysis for detecting early glaucomatous changes in ocular hypertension using optical coherence tomography.

PURPOSE: To compare symmetry analysis of the retinal nerve fiber layer (RNFL) in ocular-hypertensive, normal, and glaucomatous eyes using optical coherence tomography (OCT). METHODS: Thirty-three consecutive ocular-hypertensive patients (33 eyes), 25 normal volunteers (25 eyes), and 35 open-angle glaucoma patients (35 eyes) were enrolled in this study. Circular OCT scans were obtained using a diameter of 3.4 mm around the optic disc. RNFL thickness was measured, and a symmetry analysis was performed using symmetry ratios. To calculate the symmetry ratios, the circle was divided into the superior and inferior hemiretina. The superior hemiretina was further subdivided into three (area I, temporal 45 degrees; area II, superior 90 degrees; and area III, nasal 45 degrees ) or five (with areas 1-5, each spanning 36 degrees ) zones. The symmetry ratios were defined as the ratios comparing the RNFL thickness within each of the zones with that in the analogous zone in the inferior hemiretina. RESULTS: RNFL thickness measurements could distinguish glaucomatous eyes from other groups, but could not distinguish ocular-hypertensive from normal eyes. However, the symmetry analysis revealed differences between ocular-hypertensive and normal eyes in area II (mean +/- SD, 0.77 +/- 0.16 vs. 0.85 +/- 0.12, P = 0.0379). CONCLUSIONS: Early glaucomatous RNFL changes might exist in some areas of ocular-hypertensive eyes, and a symmetry analysis may be a useful method for detecting these changes.

Supraciliochoroidal fluid in the eyes indicates good intraocular pressure control despite absence of obvious filtering bleb after trabeculectomy.

PURPOSE: To examine the presence of supraciliochoroidal fluid (SCF) by ultrasound biomicroscopy in posttrabeculectomy eyes that show good intraocular pressure (IOP) control despite the absence of an obvious filtering bleb. PATIENTS AND METHODS: Eyes were selected retrospectively according to the following criteria: IOP < 15 mm Hg, no antiglaucoma medication, no filtering bleb or a flattened bleb without microcystic spaces, and no ophthalmoscopic choroidal detachment after trabeculectomy with mitomycin C. The SCF was examined using 50-MHz ultrasound biomicroscopy (Zeiss-Humphrey). RESULTS: Ultrasound biomicroscopy detected SCF in five (63%) of eight eyes that met the study criteria. The extent of SCF in two of the eyes was four quadrants and one or two quadrants in three eyes. CONCLUSION: The presence of the SCF may explain increased uveoscleral outflow and may represent an IOP-lowering mechanism after trabeculectomy with mitomycin C, especially when IOP control is good and a filtering bleb is not obvious.

Immunohistochemical localization of amino acids in the diabetic retina of Goto-Kakizaki rats.

The Goto-Kakizaki (GK) rat is a spontaneous model of non-insulin-dependent diabetes mellitus without obesity and diabetic retinopathy. We examined the retinal distribution of L-glutamate, gamma aminobutyric acid (GABA), glycine, and L-aspartate as neurotransmitters in the GK rat retina, using an immunohistochemical method with high-affinity antibodies. The retinal structures in the GK rats were the same as the controls. However, in the GK rats, immunoreactivity of L-glutamate and GABA was observed in the Müller and photoreceptor cells in addition to the immunoreactivity in normal rats. There was no change in glycine distribution between GK rats and controls. In the GK rats, L-aspartate accumulated in the inner segment of the photoreceptor cells in addition to the normal distribution. We consider that these immunoreactivity patterns in the GK rat retina might be induced by ischemia associated with diabetes mellitus.