Aqueous Flare Changes in Ex-PRESS Glaucoma Shunt Eyes After 4.7 Tesla High-Field Magnetic Resonance Imaging.

Purpose: Ex-PRESS glaucoma shunt stainless steel devices have been used worldwide for glaucoma treatment. The purpose of this study was to evaluate the safety of high-field magnetic resonance imaging (MRI) for Ex-PRESS-inserted eyes. Methods: Using rabbits, we performed Ex-PRESS shunt surgery in one eye in each rabbit and divided the rabbits into MRI and non-MRI groups. In the MRI group, 1 week after Ex-PRESS shunt surgery under low specific absorption rate (SAR) conditions and 1 week later under high SAR conditions, high-field 4.7-Tesla MRI was performed. Aqueous flare counts were measured before and after the Ex-PRESS shunt surgery and each MRI examination. The rabbits in the non-MRI group received only general anesthesia, and aqueous flare counts were measured as for those of the MRI group. Aqueous flare counts were expressed in photon counts per millisecond. Results: No dislocation of the Ex-PRESS shunt device was observed after MRI. The flare count ratio (MRI/non-MRI) in Ex-PRESS-inserted eyes 2 hours after high SAR MRI increased significantly compared with that before MRI (0.8 ± 0.3 vs 2.7 ± 0.8; pre-high SAR MRI vs 2 hours after high SAR MRI, respectively; P = 0.01). The day after MRI, the flare count improved spontaneously to the same level as that before MRI. Conclusions: Our results indicate that high-field MRI can be performed relatively safely after Ex-PRESS shunt surgery. Translational Relevance: This study demonstrates the safety of high-field MRI for Ex-PRESS-inserted eyes using a rabbit model.

Prosocial and antisocial choices in a monogamous cichlid with biparental care.

Human society is cooperative and characterized by spontaneous prosociality. Comparative studies on endotherm vertebrates suggest that social interdependence causes the evolution of proactive prosociality. To test the generality of this hypothesis, we modify a prosocial choice task for application to the convict cichlid, Amatitlania nigrofasciata, a monogamous fish with biparental care and a strong pair bond. We also affirm that male subjects learn to favor prosocial choices when their mates are the recipients in a neighboring tank. When the neighboring tank is empty, males choose randomly. Furthermore, in the absence of their mates, males behave prosocially toward a stranger female. However, if the mate of the subjects is also visible in the third tank, or if a male is a potential recipient, then subjects make antisocial choices. To conclude, fish may show both spontaneous prosocial and antisocial behaviors according to their social relationships with conspecifics and the overall social context.

Ocular hypotensive effects of a Rho-associated protein kinase inhibitor in rabbits.

PURPOSE: Ripasudil is a novel Rho-associated protein kinase inhibitor that is used to treat ocular hypertension. However, the comparison of the intraocular pressure (IOP)-lowering effects between ripasudil alone and other ocular hypotensive drugs has not been studied thoroughly. The purpose of this study is to examine the ocular hypotensive effects of 0.4% ripasudil, 2% pilocarpine, 0.5% timolol and 0.1% dorzolamide in rabbits. We also studied the IOP changes when 0.4% ripasudil was combined with 2% pilocarpine, 0.5% timolol or 0.1% dorzolamide. METHODS: One drop of saline solution, 0.4% ripasudil, 0.5% timolol, 2% pilocarpine or 1% dorzolamide or a combination of these agents was applied topically to the left eyes of eight healthy albino rabbits. Posttreatment changes in the IOP of albino rabbits were monitored using a rebound tonometer over a 5-h time course. Changes in IOP after application of saline served as the control. One-way analysis of variance and Dunnett's post hoc tests were used for statistical analyses. RESULTS: After topical instillation, 0.4% ripasudil resulted in significant decreases in IOP at 0.5 and 1 h compared with the control group. Treatment with timolol, pilocarpine or dorzolamide had no significant effect on IOP. Treatment with timolol, pilocarpine or dorzolamide in combination with ripasudil resulted in significant reductions in IOP at 1 h. However, none of these agents enhanced the IOP-lowering effects of ripasudil. CONCLUSION: Ripasudil has stronger IOP-lowering effects than timolol, pilocarpine or dorzolamide hypotensive agents in our rabbit model. Addition of timolol, pilocarpine or dorzolamide did not enhance the IOP-lowering effects of ripasudil alone.

Effects of topical adrenergic agents on prostaglandin E2-induced aqueous flare and intraocular pressure elevation in pigmented rabbits.

PURPOSE: To evaluate the effects of signals through adrenergic receptors on the changes in the aqueous flare and intraocular pressure (IOP) induced by topical prostaglandin E2 (PGE2) in pigmented rabbits. METHODS: Adrenergic agents were applied topically to pigmented Dutch rabbits, and PGE2 was then applied to induce an increase in the aqueous flare and IOP. The degree of aqueous flare was measured with a laser flare meter, and the IOP was measured with a rebound tonometer. Measurements were made every 30 min after the PGE2 had been applied for 2 h and at 4.0 and 4.5 h. Repeated measure analysis of variance and Dunnett's post hoc tests were used for the statistical analyses. RESULTS: The topical application of PGE-2 increased the aqueous flare for more than 4.5 h. The topical instillation of 1.0 % apraclonidine significantly inhibited the increase in the PGE2-induced aqueous flare by 75.1 %, of 0.1 % brimonidine by 57.2 %, of 0.04 % dipivefrin by 57.4 %, and a combination of 0.1 % brimonidine and 5 % phenylephrine by 78.9 %. Topical 5.0 % phenylephrine and 0.05 % isoproterenol had little effect on the aqueous flare elevation induced by PGE2. The IOP increased 0.5 h after the topical application of PGE-2. Topical 1.0 % apraclonidine, 0.1 % brimonidine, 0.1 % dipivefrin, and the combination of 0.1 % brimonidine and 5.0 % phenylephrine significantly inhibited the PGE2-induced IOP elevation. However, topical 5.0 % phenylephrine and 0.05 % isoproterenol did not significantly inhibit the IOP elevation caused by PGE2. CONCLUSIONS: Signaling by the α2 receptor inhibits both the PGE2-induced flare and IOP elevation caused by topical PGE2 application.

Antimicrobial action from a novel porphyrin derivative in photodynamic antimicrobial chemotherapy in vitro.

Efforts to identify improved treatments for corneal infection include the development of photodynamic antimicrobial chemotherapy (PACT). We evaluated the antimicrobial effect of PACT with a novel porphyrin derivative, TONS 504, and a novel light system on methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). Bacteria were irradiated with a light-emitting diode (LED) at energies of 10, 20, or 30 J/cm(2) in the presence of various concentrations of TONS 504. Bacterial viability was assessed at 30 min and 24 h after irradiation by determination of colony formation on agar plates. PACT inhibited the growth of both MSSA and MRSA as early as 30 min after light exposure. Complete inhibition of bacterial growth was apparent at 24 h after irradiation at a TONS 504 concentration of 1 mg/L and LED energies of ≥10 J/cm(2) or a TONS 504 concentration of 0.5 mg/L and LED energies of ≥20 J/cm(2) for MSSA, and at a TONS 504 concentration of 10 mg/L and LED energies of ≥10 J/cm(2) or of a TONS 504 concentration of 1 mg/L and LED energies of ≥20 J/cm(2) for MRSA. Bacterial growth was unaffected by TONS 504 in the absence of irradiation or by irradiation in the absence of TONS 504. Our results thus demonstrate the antimicrobial efficacy of PACT with TONS 504 and a LED against both MSSA and MRSA in vitro, and they therefore provide a basis for further investigation of this system as a potential treatment for corneal infection.

Matrix metalloproteinase and cytokine expression in Tenon fibroblasts during scar formation after glaucoma filtration or implant surgery in rats.

Failure of surgery for glaucoma is usually due to post-surgical scarring (fibrosis), a process in which fibroblasts play a prominent role. We investigated the molecular mechanisms of such scarring by examining the expression of matrix metalloproteinases and cytokines in Tenon fibroblasts isolated from rats after glaucoma surgery. Filtration surgery was performed in one eye and implant surgery in the other; and Tenon fibroblasts were isolated from the tissue surrounding the bleb after surgery. The cells were cultured and examined for the expression of matrix metalloproteinases (MMPs) by reverse transcription-polymerase chain reaction, immunoblot and gelatin zymographic analyses. Culture supernatants were also assayed for cytokines with a multiplex array. The amounts of MMP-1 and MMP-3 mRNAs and proteins were greater in cells isolated after implant surgery than in those isolated after filtration surgery, with the progression of scar formation being more complete after the former surgery. The secretion of interleukin-6 (IL-6) by cells isolated after filtration surgery was greater than that for cells isolated after implant surgery. Depletion of IL-6 by RNA interference in cells isolated after filtration surgery increased the expression of MMP-1 and MMP-3 in these cells. These results thus suggest that the expression of MMP-1 and MMP-3 in Tenon fibroblasts is regulated by IL-6 during, and may play an important role in, scar formation after glaucoma surgery.

Differential expression of semaphorin 3A and its receptors during mouse retinal development.

Semaphorins not only function in axon guidance during development but also contribute to various other biological processes. We have now examined the expression of semaphorin 3A (Sema3A) and its receptor components neuropilin 1 (Npn1) and plexin A (PlxA) during development of the mouse retina. Immunohistofluorescence analysis revealed that the expression patterns of Sema3A and Npn1 were similar during embryonic and postnatal development. The expression pattern of PlxA was also similar to those of Sema3A and Npn1 during embryonic and early postnatal (before eye opening) developments. However, the pattern of PlxA expression changed markedly after eye opening, with the expression disappearing from the optic nerve and increasing in intensity in the retinal pigment epithelium. Immunoprecipitation analysis showed that Sema3A interacted with PlxA in the retinal pigment epithelial cell line ARPE19 but not in the retinal ganglion cell line RGC5, whereas the opposite pattern of association was apparent for Sema3A and Npn1. Given that atmospheric oxygen is thought to play a role in the differentiation and maintenance of various ocular cell types, our results suggest that Sema3A-PlxA signalling activated by an effect of ambient oxygen on PlxA expression may contribute to differentiation of the retinal pigment epithelium.