Compromised Blood Flow in the Optic Nerve Head after Systemic Administration of Aldosterone in Rats: A Possible Rat Model of Retinal Ganglion Cell Loss.

PURPOSE: To investigate the optic nerve head (ONH) blood flow, retinal vessel diameters, and retinal ganglion cell (RGC) loss after systemic administration of aldosterone in rats. METHODS: Aldosterone (80 µg/kg/day) or vehicle was administered using an osmotic minipump in Brown Norway rats. The mean blur rate in the vessel (MV) and tissue (MT) regions and retinal vessel diameters in the ONH were measured by laser speckle flowgraphy before and 1, 2, and 4 weeks after administration of aldosterone or vehicle. Intraocular pressure (IOP), blood pressure, and heart rate were recorded. The retrogradely labeled RGCs were counted in the retinal flatmounts prepared 5 weeks after treatment. RESULTS: The MV and MT in the aldosterone group significantly decreased at 2 and 4 weeks (MV: 2 weeks, p = 0.001, 4 weeks, p < 0.001; MT: 2 weeks, p = 0.02, 4 weeks, p = 0.03). The artery and vein diameters significantly decreased at 1, 2, and 4 weeks in the aldosterone group (all p < 0.001). The MV, MT, and vessel diameters remained unchanged in the vehicle group. Other parameters did not change over time in either group. RGC counts were significantly lower in the aldosterone group than in the vehicle group (p < 0.001). CONCLUSIONS: ONH blood flow decreased following retinal vessel constriction without changes in IOP or blood pressure in a possible rat model of RGC loss by systemic administration of aldosterone.

Effects of ripasudil, a rho kinase inhibitor, on blood flow in the optic nerve head of normal rats.

PURPOSE: To evaluate the effect of topically administrated ripasudil, a rho kinase inhibitor, on blood flow in the optic nerve head (ONH) of normal rats. METHODS: Ripasudil (0.4%) or placebo was administered in the right eye of normal Brown Norway rats in a double-blind manner. Laser speckle flowgraphy was measured in the ONH of the right eye 20 or 40 min after a single instillation and before and after 7 or 14 days of twice daily instillation. Mean blur rate was evaluated in the total area (MA), the vessel region (MV), and the tissue region (MT). Intraocular pressure (IOP), blood pressure, ocular perfusion pressure (OPP), and heart rate were also recorded at each time point. RESULTS: After a single instillation, MV was significantly larger at 40 min than 20 min in the ripasudil group (P = 0.044) and was significantly lower in the placebo group (P = 0.023). MA and MV 40 min after instillation were significantly larger in the ripasudil group than in the placebo group (P = 0.022 and P = 0.006, respectively). After continuous instillation, MA and MV in the ripasudil group significantly increased from baseline after 7 and 14 days of treatment (both P < 0.05) and MA, MV, and MT were significantly higher than in the placebo group (MA: 7 and 14 days, P < 0.01; MV: 7 days, P = 0.003, and 14 days, P = 0.012; MT: 7 days, P = 0.046). There were no significant changes in IOP, blood pressure, or OPP after single or continuous instillation. CONCLUSIONS: Topical instillation of ripasudil increased blood flow around the ONH in the eyes of normal rats.

Longitudinal Changes in Optic Nerve Head Blood Flow in Normal Rats Evaluated by Laser Speckle Flowgraphy.

PURPOSE: To investigate longitudinal changes in mean blur rate (MBR) measured by laser speckle flowgraphy (LSFG) in the rat optic nerve head (ONH), and the reproducibility of MBR. METHODS: Rats were dilated under general anesthesia. Intraocular pressure (IOP), blood pressure, ocular perfusion pressure (OPP), heart rate, and LSFG were measured 30 minutes later. Mean blur rate in the ONH was determined using LSFG-Micro and was subdivided into MBR of the total area (MA), vessel region (MV), and tissue region (MT). Mean blur rate measurements were repeated at 10, 11, 13, 19, and 20 weeks, then every 5 weeks until 60 weeks of age. Intrasession repeatability, intrasession reproducibility, and intersession reproducibility were evaluated. RESULTS: Coefficient of variation of MBR was 0.3 to 6.2%, 1.3 to 5.2%, and 5.8 to 30.4% for intrasession repeatability, intrasession reproducibility, and intersession reproducibility, respectively. Mean blur rate of the total area, MV, and MT increased similarly until 19 weeks of age, but stabilized thereafter until 60 weeks. Mean blur rate of the total area in the inferior quadrant was significantly higher than in the temporal quadrant from 19 to 55 weeks. These changes exceeded a range of corresponding coefficient of reproducibility. There were no significant changes in IOP, blood pressure, or OPP during the experimental period. CONCLUSIONS: Mean blur rate in the rat ONH changed over time, increased from 10 to 19 weeks of age, then stabilized until 60 weeks. Mean blur rate of the total area exhibited regional differences: higher in the inferior quadrant than in the temporal quadrant. Laser speckle flowgraphy-Micro may provide reliable information for evaluating longitudinal changes of rat ONH blood flow.

[A case successfully treated by desensitization for paclitaxel-associated hypersensitivity reactions].

We report a case of a 56-year-old woman with hypersensitivity reactions (HSRs) symptoms against paclitaxel (PTX) which were suppressed by pre-injection of a low-dose of PTX before the full-dose injection. She received PTX chemotherapy (120 mg/body/week for three weeks on the 1st, 8th, and 15th day, followed by no drug for one week) in October 2004 for right breast cancer. However, continuation of the therapy was in jeopardy due to respiratory difficulties and facial flushing, considered to be HSRs symptoms, on day 15. However,we were able to continue the PTX chemotherapy by administering a low-dose pre-injection (2 mg/100 mL/30 min) before the full-dose injection. After that, HSRs symptoms were observed, but we were able to administer another low-dose pre-injection (1 mg/100 mL/30 min). Three courses of chemotherapy were successfully performed, followed by radical surgery in February 2005. A pathological complete response (pCR) of the maintumor was achieved. We suggest that pre-injection of a low-dose of PTX before the full-dose injection may be effective for prevention of the onset of HSRs symptoms.

Effect of protease-activated receptor-2 deficiency on allergic dermatitis in the mouse ear.

To investigate the involvement of protease-activated receptor-2 (PAR-2) in allergic dermatitis, we generated PAR-2-deficient (PAR-2(-/-)) mice. Ear thickness, contact hypersensitivity (CH) induced by topical application of picryl chloride (PC) or oxazolone (Ox) after sensitization, and vascular permeability after ear passive cutaneous anaphylaxis (PCA) were compared between wild-type (WT) and PAR-2(-/-) mice. Ear thickness was almost the same in untreated WT and PAR-2(-/-) mice. Topical application of PC or Ox thickened the ears at 6, 24 and 48 h after challenge with a peak at 24 h in WT mice. In PAR-2(-/-) mice, the ear swelling induced by both PC and Ox was suppressed at every time point, and significant inhibition was found at 24 h in PC-induced CH and at 24 and 48 h in Ox-induced CH. Histopathological observation of the ears at 24 h after challenge revealed that PC- or Ox-induced ear edema and infiltration of inflammatory cells in WT mice were greatly attenuated in PAR-2(-/-) mice. The vascular permeability in the ears after PCA was not different between WT and PAR-2(-/-) mice. These results strongly suggest that PAR-2 plays a crucial role in type IV allergic dermatitis but not in type I allergic dermatitis.