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.

Multi-Level Processes and Retina–Brain Pathways of Photic Regulation of Mood

Light exerts powerful biological effects on mood regulation. Whereas the source of photic information affecting mood is well established at least via intrinsically photosensitive retinal ganglion cells (ipRGCs) secreting the melanopsin photopigment, the precise circuits that mediate the impact of light on depressive behaviors are not well understood. This review proposes two distinct retina–brain pathways of light effects on mood: (i) a suprachiasmatic nucleus (SCN)-dependent pathway with light effect on mood via the synchronization of biological rhythms, and (ii) a SCN-independent pathway with light effects on mood through modulation of the homeostatic process of sleep, alertness and emotion regulation: (1) light directly inhibits brain areas promoting sleep such as the ventrolateral preoptic nucleus (VLPO), and activates numerous brain areas involved in alertness such as, monoaminergic areas, thalamic regions and hypothalamic regions including orexin areas; (2) moreover, light seems to modulate mood through orexin-, serotonin- and dopamine-dependent pathways; (3) in addition, light activates brain emotional processing areas including the amygdala, the nucleus accumbens, the perihabenular nucleus, the left hippocampus and pathways such as the retina–ventral lateral geniculate nucleus and intergeniculate leaflet–lateral habenula pathway. This work synthetizes new insights into the neural basis required for light influence mood

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.

Challenges in the Intraoperative Consultation of Low-Grade Epilepsy-Associated Neuroepithelial Tumors by Cytomorphology in Squash Preparations

<b><i>Introduction:</i></b> Low-grade epilepsy-associated neuroepithelial tumors (LEATs) create a diagnostic challenge in daily practice and intraoperative pathological consultation (IC) in particular. Squash smears are extremely useful in IC for accurate diagnosis; however, the knowledge on cytopathologic features of LEATs is based on individual case reports. Here, we discuss the 3 most common and well-established entities of LEATs: ganglioglioma (GG), dysembryoplastic neuroepithelial tumor (DNT), and papillary glioneuronal tumor (PGNT). <b><i>Methods:</i></b> Thirty patients who underwent surgery for GG, DNT, and PGNT between 2001 and 2021 were collected. Squash smears prepared during intraoperative consultation were reviewed by 1 cytopathologist and an experienced neuropathologist. <b><i>Results:</i></b> Among the 30 tumors, 16 (53.3%) were GG, 11 (36.6%) DNT, and 3 (10%) PGNT. Cytomorphologically, all of the 3 tumor types share 2 common features such as dual cell population and vasculocentric pattern. GG smears were characteristically composed of dysplastic ganglion cells and piloid-like astrocytes on a complex architectural background of thin- to thick-walled vessels. DNT, on the other hand, showed oligodendroglial-like cells in a myxoid thin fibrillary background associated with a delicate capillary network. Common cytological features of PGNT were hyperchromatic cells with narrow cytoplasm surrounding hyalinized vessels forming a pseudopapillary pattern and bland cells with neuroendocrine nuclei dispersed in a neuropil background. <b><i>Conclusion:</i></b> A higher diagnostic accuracy can be obtained when squash smears are applied with frozen sections. However, it is important to integrate clinical and radiologic features of the patient as well as to know the cytopathologic features of the LEAT spectrum in the context of differential diagnosis to prevent misinterpretation in the IC.

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

A Novel Tree Shrew Model of Diabetic Retinopathy

Existing animal models with rod-dominant retinas have shown that hyperglycemia injures neurons, but it is not yet clearly understood how blue cone photoreceptors and retinal ganglion cells (RGCs) deteriorate in patients because of compromised insulin tolerance. In contrast, northern tree shrews (Tupaia Belangeri), one of the closest living relatives of primates, have a cone-dominant retina with short wave sensitivity (SWS) and long wave sensitivity (LWS) cones. Therefore, we injected animals with a single streptozotocin dose (175 mg/kg i.p.) to investigate whether sustained hyperglycemia models the features of human diabetic retinopathy (DR). We used the photopic electroretinogram (ERG) to measure the amplitudes of A and B waves and the photopic negative responses (PhNR) to evaluate cone and RGC function. Retinal flat mounts were prepared for immunohistochemical analysis to count the numbers of neurons with antibodies against cone opsins and RGC specific BRN3a proteins. The levels of the proteins TRIB3, ISR-1, and p-AKT/p-mTOR were measured with western blot. The results demonstrated that tree shrews manifested sustained hyperglycemia leading to a slight but significant loss of SWS cones (12%) and RGCs (20%) 16 weeks after streptozotocin injection. The loss of BRN3a-positive RGCs was also reflected by a 30% decline in BRN3a protein expression. These were accompanied by reduced ERG amplitudes and PhNRs. Importantly, the diabetic retinas demonstrated increased expression of TRIB3 and level of p-AKT/p-mTOR axis but reduced level of IRS-1 protein. Therefore, a new non-primate model of DR with SWS cone and RGC dysfunction lays the foundation to better understand retinal pathophysiology at the molecular level and opens an avenue for improving the research on the treatment of human eye diseases.

Mechanism of Propofol-Lidocaine Hydrochloride Nano-Emulsion on Retinal Ganglion Cytopathic Effect in Diabetic Rats

The study drew attention to the influence mechanism of propofol and lidocaine hydrochloride nanoemulsion (NE) in the retinal ganglion cell pathology in diabetic rats. Specifically, the propofollidocaine hydrochloride NE was prepared using the emulsification method. The microscope and laser particle size analyser were used to observe the morphology and particle size of NE, respectively. Also, the viscosity of the NE and the recovery rate of the main ingredient were explored. 45 adult male Wistar rats were randomly divided into control group (PBS control), model group (diabetes model), and test group (diabetes model+propofol-lidocaine hydrochloride NE), with 15 rats in each group. The three groups were compared for the blood glucose, body weight, TNF-α and IL-1β mRNA levels in retinal tissue, and the number and apoptosis rate of ganglion cells. It was found that the average particle size of the NE was 89.76 nm, the maximum absorption wavelength was 280.0 nm, and the viscosity was 106.49 N/m/s. The average recovery rate of propofol in NE was 99.91%, and that of lidocaine hydrochloride was 99.80%. At 12th week after modeling, the blood glucose of the test group was lower versus the model group (P < 0.05); the blood glucose and body weight of rats in the control group were lower than those in the other two groups (P < 0.001). The test group exhibited lower mRNA levels of TNF-α and IL-1β and apoptosis index of retinal ganglion cells versus the model group (P < 0.05). The model group showed a lower number of retinal ganglion cells versus the other two groups (P < 0.05). It was inferred that propofol-lidocaine hydrochloride NE of a small particle size and good syringeability can notably reduce blood glucose, TNF-α and IL-1β mRNA levels, and retinal ganglion cell apoptosis index, and at the same time increase the number of retinal ganglion cells.