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.

Panoramic visual statistics shape retina-wide organization of receptive fields

Visual systems have adapted to the structure of natural stimuli. In the retina, center-surround receptive fields (RFs) of retinal ganglion cells (RGCs) appear to efficiently encode natural sensory signals. Conventionally, it has been assumed that natural scenes are isotropic and homogeneous; thus, the RF properties are expected to be uniform across the visual field. However, natural scene statistics such as luminance and contrast are not uniform and vary significantly across elevation. Here, by combining theory and novel experimental approaches, we demonstrate that this inhomogeneity is exploited by RGC RFs across the entire retina to increase the coding efficiency. We formulated three predictions derived from the efficient coding theory: (i) optimal RFs should strengthen their surround from the dimmer ground to the brighter sky, (ii) RFs should simultaneously decrease their center size and (iii) RFs centered at the horizon should have a marked surround asymmetry due to a stark contrast drop-off. To test these predictions, we developed a new method to image high-resolution RFs of thousands of RGCs in individual retinas. We found that the RF properties match theoretical predictions, and consistently change their shape from dorsal to the ventral retina, with a distinct shift in the RF surround at the horizon. These effects are observed across RGC subtypes, which were thought to represent visual space homogeneously, indicating that functional retinal streams share common adaptations to visual scenes. Our work shows that RFs of mouse RGCs exploit the non-uniform, panoramic structure of natural scenes at a previously unappreciated scale, to increase coding efficiency.

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.

Evidence for Menopause as a Sex-Specific Risk Factor for Glaucoma

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive loss of visual function and retinal ganglion cells (RGC). Current epidemiological, clinical, and basic science evidence suggest that estrogen plays a role in the aging of the optic nerve. Menopause, a major biological life event affecting all women, coincides with a decrease in circulating sex hormones, such as estrogen. While 59% of the glaucomatous population are females, sex is not considered a risk factor for developing glaucoma. In this review, we explore whether menopause is a sex-specific risk factor for glaucoma. First, we investigate how menopause is defined as a sex-specific risk factor for other pathologies, including cardiovascular disease, osteoarthritis, and bone health. Next, we discuss clinical evidence that highlights the potential role of menopause in glaucoma. We also highlight preclinical studies that demonstrate larger vision and RGC loss following surgical menopause and how estrogen is protective in models of RGC injury. Lastly, we explore how surgical menopause and estrogen signaling are related to risk factors associated with developing glaucoma (e.g., intraocular pressure, aqueous outflow resistance, and ocular biomechanics). We hypothesize that menopause potentially sets the stage to develop glaucoma and therefore is a sex-specific risk factor for this disease. Graphical Abstract

Preservative free travoprost and timolol fixed combination in the initial treatment of primary glaucoma: an assessment of hypotensive efficiency and safety

Purpose. To evaluate the efficacy and safety of Travapress Duo with respect to hypotensive results, changes in functional parameters, and adverse reactions. Material and methods. 30 patients aged 65–75 (averagely 71.3 ± 3.2 years) with a newly diagnosed primary open-angle glaucoma (POAG) received Travapress Duo in the evening, once a day. Goldman tonometry was performed during the screening, then 1 week, 1 month and 3 months from the treatment start. Static perimetry and optical coherence tomography (OCT) were performed before treatment and at the end of the 3rd month since the treatment start. Adverse events were recorded at each stage of the study.Results. As a result of a 3 month long therapy with Travapress Duo, a significant decrease in IOP was noted starting from the 1st week of instillations (by 34 %), after 1 month, by 35 % and after 3 months of observation by 36 %. By the end of the 3rd month of treatment, we noted an insignificant increase in visual acuity, a positive dynamic of the standard deviation and the standard deviation pattern, as well as OCT indicators, such as average thickness of the layer of retinal nerve fibers and the layer of retinal ganglion cells in the macula, stabilization of the thickness of the retinal ganglion cell complex layer and the size of the inner plexiform layer. One patient complained of discomfort and hyperemia by the end of the 1st week of drug instillation. No systemic side effects were noted during the follow-up, and in no case drug withdrawal was require. Conclusion. The preservative-free Travapress Duo drug displayed a high hypotensive efficacy, reducing the IOP to 36% of the initial value. The hypotensive effect was accompanied by indirect neuroprotection, which manifested itself in the positive changes observable in the results of functional studies with varying degrees of reliability. Travapress Duo is characterized by a low level of local side effects and can be recommended for both for the initial and long-term therapy of primary glaucoma of developed and advanced stages.