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Background and objectives This study aimed to compare the efficacy of fluorescein angiography (FA)-guided and indocyanine green angiography (ICGA)-guided half-time photodynamic therapy (PDT) for central serous chorioretinopathy (CSC). Subjects and methods Medical records of 61 eyes of 61 CSC patients who underwent half-time PDT were retrospectively reviewed. The irradiation area was determined using information from FA or ICGA with physicians’ discretion. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SCT), and resolution of subretinal fluid (SRF) were evaluated at baseline and 1, 3, 6, and 12 months after PDT. Results A total of 29 and 32 eyes received FA-guided PDT (irradiation area, 2898.3 ± 705.7 μm) and ICGA-guided PDT (irradiation area, 4993.8 ± 333.1 μm), respectively. A significant improvement in the mean BCVA was found at 1 month in the FA-guided group (P = 0.02), but not in the ICGA-guided group (P = 0.88). BCVA was significantly improved in both groups at 3, 6, and 12 months with no significant intergroup difference at any time points. CRT and SCT were significantly reduced in both groups at all time points with no significant intergroup differences. No significant intergroup differences were observed in the rate of recurrence and persistent SRF. However, there was a significant difference between groups in the rate of recurrence and/or persistent SRF (P = 0.04). Multivariate analysis revealed that choice of FA-guided was significantly associated with recurrence and/or persistent SRF (P = 0.04). Conclusion Half-time PDT with ICGA-guided irradiation spot might be more effective than that with FA-guided in treating CSC patients in complete resolution of SRF.

Aquaporin 9 (AQP9), an aquaglyceroporin, is not only permeable to water but also to non-charged solutes, such as lactate. Lactate can be an energy source for retinal neurons. This study aimed to evaluate the effect of the downregulation of AQP9 expression on the survival rates and reactive oxygen species accumulation in RGC-5 cells cultured in a medium containing lactate. The Live/Dead assay revealed that the cell death rate of RGC-5 cells transfected with the control siRNA (siControl) was 3.65%±0.75% in the 5-mM glucose medium. The death rate was significantly increased by five-fold in the no glucose and 10-mM d-lactate media but not in the 10-mM l-lactate medium. In comparison, the death rate of cells transfected with siRNA targeting AQP9 (siAQP9) was 8.07%±1.01% in the 5-mM glucose medium, which was significantly increased by two-fold in the other medium conditions, indicating that the downregulation of AQP9 expression eliminated the prosurvival effect of l-lactate. Few RGC-5 cells transfected with siControl showed dichlorofluorescein (DCF) fluorescence when cultured in 5-mM glucose and 10-mM l-lactate media. However, approximately 70% of those showed DCF fluorescence when cultured in the no glucose and 10-mM d-lactate media. The downregulation of AQP9 significantly increased the DCF fluorescence rate to 50.44%±6.13% in the 10-mM l-lactate medium, whereas, it did not increase the rate in the other medium conditions. These results demonstrate that AQP9 expression is required for l-lactate to maintain retinal neuronal survival.

The impairment of mitochondrial function is an important pathogenic factor in glaucoma and other optic neuropathies in which retinal ganglion cell (RGC) death is the fundamental pathology. Syntaphilin was recently discovered as a docking protein that affects mitochondrial mobility. However, no reports have investigated the involvement of syntaphilin in the visual system. We investigated the expression of syntaphilin in the rat retina, optic nerve and brain. The expression of syntaphilin exhibited varying patterns in the visual system. Syntaphilin was expressed in retinal ganglion cells in the retina, in the cell bodies of neurons in the superior colliculus and was abundant in the astrocytes of rat optic nerves (similar to the findings that syntaphilin is expressed in human optic nerves). After optic nerve transection, which caused RGC death and axonal degeneration, quantitative real-time RT-PCR was used to assess changes in gene expression in the rat retina and optic nerve. Syntaphilin gene and protein expression in the optic nerve was downregulated 3 and 7 days after optic nerve transection. Our study suggests that syntaphilin expression in astrocytes at the optic nerve might be involved in axonal injury.

Purpose To investigate whether complement factor H ( CFH ) gene DNA variants are associated with central serous chorioretinopathy (CSCR). Design Cross-sectional study. Participants A case-control group of 140 CSCR subjects and 2 different control groups: 934 population-based controls and 335 hospital-based controls. Methods Five single-nucleotide polymorphisms (SNPs) in CFH (rs3753394, rs800292, rs2284664, rs1329428, and rs106548) were evaluated for association with CSCR in 2 separate association analyses comparing CSCR subjects with 2 different control groups. Genotyping was performed using TaqMan technology (Applied Biosystems, Foster City, CA). Main Outcome Measures Allele and haplotype frequencies of the 5 variants in the CFH region. Results Highly statistically significant associations with CSCR were found for the 5 SNPs. The strongest association was observed with rs1329428 (allelic P = 6.44×10 −6 ; odds ratio, 1.79; 95% confidence interval [CI], 1.39–2.31, cases vs. population-based controls), which accounted for 35.5% of the population-attributable fraction for CSCR. Consistent with the analysis, rs1329428 showed the strongest disease association (allelic P = 1.00×10 −5 ; odds ratio, 1.89; 95% CI, 1.42–2.50) in comparing cases with hospital-based controls. The second most strongly associated SNP, rs1065489, was correlated highly with the most strongly associated SNP, rs1329428 ( r 2 = 0.77), and their effects could not be distinguished statistically from each other. A conditional logistic regression analysis revealed that the 2 highly correlated SNPs, rs1329428 and rs1065489, account for the association signals detected at the CFH locus. Conclusions We identified a novel association between CSCR and common CFH polymorphisms. Our findings support the involvement of CFH in the pathogenesis of CSCR; exploration of the role of CFH could yield important insights into the biological mechanisms underlying CSCR. Our identification of common CFH variants as susceptibility elements for CSCR will open new avenues for research, leading to a better understanding of CSCR pathogenesis and ultimately to the development of improved therapeutic approaches.

Aquaporin 9 (AQP9), an aquaglyceroporin belonging to the AQP water channel family, is permeable not only to water but also to noncharged solutes such as lactate. In neurons, lactate presumably acts as an energy substrate and as a source of NADH (the reduced form of nicotinamide adenine dinucleotide), a scavenger of reactive oxygen species (ROS). We previously reported that retinal ganglion cells (RGCs) express AQP9 and that elevated intraocular pressure reduces AQP9 expression and increases death of neurons in the retinal ganglion cell layer of rodents. In the present study, we investigated the association of AQP9 expression with serum deprivation-induced death of RGC-5 cells and with death of neurons in the rat retinal ganglion cell layer after optic nerve transection (ONT). The effect of AQP9 RNA interference on serum deprivation-induced apoptosis, ROS accumulation, and the NAD(+)/NADH ratio in RGC-5 cells was examined. Both serum deprivation and ONT significantly reduced AQP9 protein expression in RGCs and increased the rate of RGC death. Retinal AQP9 gene expression also declined after ONT. Down-regulation of AQP9 significantly increased apoptosis, ROS accumulation, and the NAD(+)/NADH ratio in the RGC-5 cells. These findings suggest that AQP9 loss adversely affects survival of RGCs, at least partly because of decreased transport of lactate as a substrate for energy and/or ROS scavenger.

Objective This study compared the effects of intraocular injections of ranibizumab (RBZ) and bevacizumab (BVZ) in transgenic mouse models in which human vascular endothelial growth factor (VEGF) causes subretinal neovascularization (NV) or exudative retinal detachment. Design Randomized trials in animal models. Participants Transgenic mice in which the rhodopsin promoter drives expression of human VEGF in photoreceptors ( rho/VEGF mice) and double transgenic mice with doxycycline-inducible expression of human VEGF in photoreceptors ( Tet/opsin/VEGF mice). Methods Rho/VEGF mice received intraocular injections of RBZ, BVZ, or vehicle, and after various time periods the area of subretinal NV was measured. Tet/opsin/VEGF mice were given an intraocular injection of RBZ, BVZ, or vehicle, and after 5 days of doxycycline treatment the presence or absence of retinal detachment was determined. Main Outcome Measures Area of subretinal NV per retina in rho/VEGF mice and the occurrence of retinal detachment in Tet/opsin/VEGF mice. Results In rho/VEGF mice, intraocular injections of RBZ or BVZ strongly suppressed subretinal NV, but the duration of effect was greater for BVZ. Three injections of 10 μg of BVZ over the course of 2 weeks not only suppressed subretinal NV in the injected eye but also caused significant suppression in the fellow eye, indicating a systemic effect. In doxycycline-treated Tet/opsin/VEGF mice, intraocular injection of 10 μg of BVZ significantly reduced the incidence of exudative retinal detachment compared with injection of 10 μg of RBZ. Injection of 25 μg of BVZ reduced the incidence of retinal detachment in both eyes. Conclusions Intraocular injections of RBZ and BVZ had similar efficacy in rho/VEGF mice, but the duration of effect was greater for BVZ. In Tet/opsin/VEGF mice, in which expression levels of human VEGF are very high and the phenotype is severe, BVZ showed greater efficacy than RBZ. In both models, higher doses or repeated injections of BVZ, but not RBZ, resulted in a systemic effect. These data suggest that BVZ is not inferior to RBZ for treatment of subretinal NV in mice and is superior in a severe model. The systemic effects of BVZ after intraocular injection deserve further study and consideration of their potential consequences. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Social support is supposed to have a positive health effect via alteration of immunity. In this study, associations between perceived social support and immune systems were examined. Immunological assessments, e.g. T cell count, Natural Killer cell count, Interferon-gamma, Interleukin-4, and psychological assessments, e.g. Generic Job Stress Questionnaire were conducted on male employees. Two-way (social support x job stressor) analyses of covariance controlling for age, smoking, alcohol consumption, and exercise revealed that there were main effects of perceived social support on NK cell counts, IL-4, and Th1/Th2 balance. On the other hand, interaction effects were observed on T cell counts and INF-gamma production in vitro. Social support affects immune function in a way that is consistent with both the direct and buffering hypotheses depending on the sources of support and the immune parameter.