Effect of Krüppel-Like Factor 7 (KLF7) on High Sugar Induced Retinal Ganglion Cell Biological Activity and Oxidative Stress

This study investigated KLF7’s effect on sugar induced retinal ganglion cells (RGCs) biological activity. The RGCs cells divided into blank group (RA), high sugar group (RB), high sugar+NC group (RC) and high sugar+KLF7 group (RD) (transfected with KLF7 mimic) followed by analysis cell proliferation by MTT, cell apoptosis by flow cytometry and protein expression by western blot and ROS level. RB and RC group showed significantly reduced KLF7 mRNA and protein level compared to RA group (P < 0.05) without different between RB and RC group (P > 0.05). RD group had significantly increased LKF7 and Sirt1 protein expression (F = 113.3, P < 0.0, 01), reduced cell proliferation (P < 0.05) and increased RGCs apoptosis rate (P < 0.05) compared with RB and RC group. After 24 h, RB and RC group presented significantly higher ROS level (P < 0.05) which was reduced in RD group (P < 0.05). In conclusion, KLF7 can change sugar induced retinal ganglion cell biological activity and reduce the oxidative stress level.

Impact of systemic steroids combined with immunosuppressive treatment on glaucomatous features in patients with systemic lupus erythematosus

AIM: To evaluate the incidence of increased intraocular pressure (IOP) and glaucomatous changes in systemic lupus erythematosus (SLE) patients in comparison with systemic steroids and immunosuppressive treatment. METHODS: Sixty-two women with SLE were divided into two groups: treated (n=47, 94 eyes) and not treated (n=15, 30 eyes) with systemic glucocorticosteroids (GC; GC-free). Twenty-one individuals in GC group were treated with immunosuppressive agents (immunomodulating and biologic). The visual acuity and IOP with ocular pulsatile amplitude (OPA) measurements, as well as scanning laser polarimetry (GDx) with nerve fiber index (NFI) measurement, spectral domain optical coherence tomography (SD-OCT) of the optic disk with retinal nerve fiber layer (RNFL) analysis and the macular region with ganglion cell analysis (GCA) were performed. RESULTS: Mean IOP values in group with combined GC and immunosuppressive therapy was 15.8±2.56 mm Hg and was significantly lower than in individuals with exclusive GC treatment (17.63±4.38 mm Hg, P=0.043). Contrary, no differences in mean IOP values between GC-free group and individuals treated with combined GC and immunosuppressive therapy were detected (P=0.563). Similarly, mean IOP in GC was 17.14±3.94 mm Hg and in GC-free patients was equal to 16.67±3.45 mm Hg (P=0.671). According to treatment regimen no statistical differences in optic disk SD-OCT for RNFL thickness, RNFL symmetry, cupping volume and the C/D ratio were observed. Similarly, no statistical differences for the mean and minimal ganglion cell layer (GCL) thickness measured in macular SD-OCT or NFI in GDx were detected. CONCLUSION: Combined immunosuppressive and systemic GC therapy in SLE patients may lower the risk of iatrogenic ocular hypertension. No relationship between treatment regimen and glaucomatous damage of optic nerve fibers in analyzed groups with SLE is detected.

Relationship of macular ganglion cell complex thickness to choroidal microvasculature drop-out in primary open-angle glaucoma

Background/aimsTo investigate the rate of ganglion cell complex (GCC) thinning in primary open-angle glaucoma (POAG) patients with and without deep-layer microvasculature drop-out (MvD).MethodsPOAG patients who had at least 1.5 years of follow-up and a minimum of three visits were included from the Diagnostic Innovations in Glaucoma Study. MvD was detected at baseline by optical coherence tomography angiography (OCT-A). Area and angular circumference of MvD were evaluated on en face choroidal vessel density images and horizontal B-scans. Rates of global and hemisphere GCC thinning were compared in MvD and non-MvD eyes using linear mixed-effects models.ResultsThirty-six eyes with MvD and 37 eyes without MvD of 63 patients were followed for a mean of 3.3 years. In 30 out of 36 eyes, MvD was localised in the inferotemporal region. While mean baseline visual field mean deviation was similar between the two groups (p=0.128), global GCC thinning was significantly faster in eyes with MvD than in those without MvD (mean differences: −0.50 (95% CI −0.83 to –0.17) µm/year; p=0.003)). Presence of MvD, area and angular circumference of MvD were independently associated with a faster rate of thinning (p=0.002, p=0.031 and p=0.013, respectively).ConclusionIn POAG eyes, GCC thinning is faster in eyes with MvD. Detection of MvD in OCT-A images can assist clinicians to identify patients who are at higher risk for central macula thinning and glaucomatous progression and may require more intensive management.

Normative data on the foveal avascular zone in a young healthy Irish population using optical coherence tomography angiography

Purpose To establish normative data on the size, shape and vascular profile of the foveal avascular zone (FAZ) in a young, healthy, Irish population, using the Cirrus 5000 HD-OCT. Certain diseases may alter FAZ appearance. Normative databases provide normal baseline values for comparison, thus improving diagnostic ability. Methods One hundred and fifty-four subjects aged 18–35 years old were recruited. Superficial FAZ area, diameter, circularity, ganglion cell layer, central macular thickness (CMT), vascular perfusion and density were measured using the Cirrus 5000. Axial length was measured with the IOL Master and blood pressure was measured using the Omron sphygmomanometer. Results Mean FAZ area was 0.22 ± 0.07 mm2, mean CMT was 263.08 ± 18.73μm. Both were larger in females than males (p = 0.022, p = 0.000). Mean vessel density and perfusion central were 14.11 ± 2.77 mm/mm2 and 24.70 ± 4.96% respectively. Both were lower in females (p = 0.010, p = 0.019). Vessel density and perfusion inner correlated positively with minimum ganglion cell layer plus inner plexiform layer (GCL + IPL) thickness (p = 0.001, p = 0.019). CMT correlated positively with vessel density and perfusion central (p = 0.000 for both) and negatively with FAZ area (p = 0.000). Conclusions This study provides normative data for FAZ appearance and vascularity for the first time in a young, healthy, Irish population, using the Cirrus 5000 HD-OCT. Establishing machine and population specific normative data, particularly in relation to vessel density and perfusion is paramount to the early identification of ocular disease using Optical Coherence Tomography Angiography.

Bax Contributes to Retinal Ganglion Cell Dendritic Degeneration During Glaucoma

The BCL-2 (B-cell lymphoma-2) family of proteins contributes to mitochondrial-based apoptosis in models of neurodegeneration, including glaucomatous optic neuropathy (glaucoma), which degrades the retinal ganglion cell (RGC) axonal projection to the visual brain. Glaucoma is commonly associated with increased sensitivity to intraocular pressure (IOP) and involves a proximal program that leads to RGC dendritic pruning and a distal program that underlies axonopathy in the optic projection. While genetic deletion of the Bcl2-associated X protein (Bax-/-) prolongs RGC body survival in models of glaucoma and optic nerve trauma, axonopathy persists, thus raising the question of whether dendrites and the RGC light response are protected. Here, we used an inducible model of glaucoma in Bax-/- mice to determine if Bax contributes to RGC dendritic degeneration. We performed whole-cell recordings and dye filling in RGCs signaling light onset (αON-Sustained) and offset (αOFF-Sustained). We recovered RGC dendritic morphologies by confocal microscopy and analyzed dendritic arbor complexity and size. Additionally, we assessed RGC axon function by measuring anterograde axon transport of cholera toxin subunit B to the superior colliculus and behavioral spatial frequency threshold (i.e., spatial acuity). We found 1 month of IOP elevation did not cause significant RGC death in either WT or Bax-/- retinas. However, IOP elevation reduced dendritic arbor complexity of WT αON-Sustained and αOFF-Sustained RGCs. In the absence of Bax, αON- and αOFF-Sustained RGC dendritic arbors remained intact following IOP elevation. In addition to dendrites, neuroprotection by Bax-/- generalized to αON-and αOFF-Sustained RGC light- and current-evoked responses. Both anterograde axon transport and spatial acuity declined during IOP elevation in WT and Bax-/- mice. Collectively, our results indicate Bax contributes to RGC dendritic degeneration and distinguishes the proximal and distal neurodegenerative programs involved during the progression of glaucoma.