The response of retinal ganglion cells to optical defocused visual stimuli in mouse retinas.

Myopia and astigmatism are two primary types of refractive errors characterized by inaccurate focusing images on the retina. This study aimed to investigate the response characteristics of Retinal Ganglion Cells (RGCs), represented by alpha (α) RGCs, when exposed to focused, simulated spherically defocused images and astigmatically defocused images projected onto mouse retinas. Negative pressure was applied to stretch the soma of RGC in vitro to simulate myopia using a 7-8 µm diameter glass microelectrode, resulting in a 5% increase in the cell's diameter. A custom-made device was utilized to project spherically (equal to ±10 and ± 20 D) and astigmatically (+6.00 D) defocused images onto the retinas. As a control for a deficient intact retinal circuit, αRGCs of connexin 36 knockout (Cx36 KO) mice were used. The response of αRGCs varied significantly in terms of spikes, excitatory postsynaptic currents (EPSCs) and capacitances under stretching conditions to mimic myopia. Significant differences in the amplitudes of EPSCs were observed in the majority of αRGCs when exposed to focused and spherically defocused images in normal and mechanically simulated myopic retinas. However, this difference was not observed in αRGCs of Cx36 KO mice. αRGCs demonstrated significant differences in response between focused and astigmatically defocused images. Once again, αRGCs of Cx36 KO mice did not display differences. αRGCs have the ability to detect focused, spherically, and astigmatically defocused images and exhibit differential responses ex vivo. Gap junction subunit Cx36 may play a crucial role in transmitting visual signals associated with developing and perceiving refractive errors.

Retinal ganglion cells encode differently in the myopic mouse retina?

The etiology of myopia remains unclear. This study investigated whether retinal ganglion cells (RGCs) in the myopic retina encode visual information differently from the normal retina and to determine the role of Connexin (Cx) 36 in this process. Generalized linear models (GLMs), which can capture stimulus-dependent changes in real neurons with spike timing precision and reliability, were used to predict RGCs responses to focused and defocused images in the retinas of wild-type (normal) and Lens-Induced Myopia (LIM) mice. As the predominant subunit of gap junctions in the mouse retina and a plausible modulator in myopia development, Cx36 knockout (KO) mice were used as a control for an intact retinal circuit. The kinetics of excitatory postsynaptic currents (EPSCs) of a single αRGC could reflect projection of both focused and defocused images in the retinas of normal and LIM, but not in the Cx36 knockout mice. Poisson GLMs revealed that RGC encoding of visual stimuli in the LIM retina was similar to that of the normal retina. In the LIM retinas, the linear-Gaussian GLM model with offset was a better fit for predicting the spike count under a focused image than the defocused image. Akaike information criterion (AIC) indicated that nonparametric GLM (np-GLM) model predicted focused/defocused images better in both LIM and normal retinas. However, the spike counts in 33% of αRGCs in LIM retinas were better fitted by exponential GLM (exp-GLM) under defocus, compared to only 13% αRGCs in normal retinas. The differences in encoding performance between LIM and normal retinas indicated the possible amendment and plasticity of the retinal circuit in myopic retinas. The absence of a similar response between Cx36 KO mice and normal/LIM mice might suggest that Cx36, which is associated with myopia development, plays a role in encoding focused and defocused images.

The Effect of Low-Dose Atropine on Alpha Ganglion Cell Signaling in the Mouse Retina.

Low-dose atropine helps to control myopia progression with few side effects. However, the impact of atropine, a non-selective muscarinic Acetylcholine (ACh) receptor antagonist, on retinal ganglion cells (RGCs) remains unclear. After immersing the cornea and adjacent conjunctiva of enucleated eyes in 0.05% (approximately 800 µM) atropine solution for 30 min, the atropine concentration reached in the retina was below 2 µM. After direct superfusion of the retina with 1 µM atropine (considering that the clinical application of 0.05% atropine eye drops will be diluted over time due to tear flow for 30 min), no noticeable changes in the morphology of ON and OFF alpha RGCs (αRGCs) were observed. Atropine affected the light-evoked responses of ON and OFF αRGCs in a dose- and time-dependent fashion. Direct application of less than 100 µM atropine on the retina did not affect light-evoked responses. The time latency of light-induced responses of ON or OFF αRGCs did not change after the application of 0.05-100 µM atropine for 5 min. However, 50 µM atropine extended the threshold of joint inter-spike interval (ISI) distribution of the RGCs. These results indicated that low-dose atropine (<0.5 µM; equal to 1% atropine topical application) did not interfere with spike frequency, the pattern of synchronized firing between OFF αRGCs, or the threshold of joint ISI distribution of αRGCs. The application of atropine unmasked inhibition to induce ON responses from certain OFF RGCs, possibly via the GABAergic pathway, potentially affecting visual information processing.

Unmasking inhibition prolongs neuronal function in retinal degeneration mouse model.

All neurodegenerative diseases involve a relatively long period of timeframe from the onset of the disease to complete loss of functions. Extending this timeframe, even at a reduced level of function, would improve the quality of life of patients with these devastating diseases. The retina, as the part of the central nervous system and a frequent site of many distressing neurodegenerative disease, provides an ideal model to investigate the feasibility of extending the functional timeframe through pharmacologic intervention. Retinitis Pigmentosa (RP) is a group of blinding diseases. Although the rate of progression and degree of visual loss varies, there is usually a prolonged time before patients totally lose their photoreceptors and vision. It is believed that inhibitory mechanisms are still intact and may become relatively strong after the gradual loss of photoreceptors in RP patients. Therefore, it is possible that light-evoked responses of retinal ganglion cells and visual information processes in retinal circuits could be "unmasked" by blocking these inhibitory mechanisms restoring some level of visual function. Our results indicate that if the inhibition in the inner retina was unmasked in the retina of the rd10 mouse (the well-characterized RP mimicking, clinically relevant mouse model), the light-evoked responses of many retinal ganglion cells can be induced and restore their normal light sensitivity. GABA A receptor plays a major role in this masking inhibition. ERG b-wave and behavioral tests of spatial vision partly recovered after the application of PTX. Hence, removing retinal inhibition unmasks signalling mediated by surviving cones, thereby restoring some degree of visual function. These results may offer a novel strategy to restore the visual function with the surviving cones in RP patients and other gradual and progressive neurodegenerative diseases.

Trends in the incidence of AIDS and epidemiological features in Tianjin, China from 2005 to 2016.

The objective of this study was to assess the epidemiological trends among patients with AIDS in Tianjin, China. A long-term surveillance study was conducted from 2005 to 2016 in Tianjin, China. All patients with AIDS registered in Tianjin from 2005 to 2016 were recruited to this study. Demographic information and clinical features were recorded. A total of 3062 patients with AIDS who were treated with antiretroviral therapy were included in this study. Among AIDS patients, men were more likely to be younger than women (age, 37.84 years vs. 43.27 years; P < 0.001). The incidence of AIDS increased by 39.6% annually over the past 12 years overall. There was the greatest increase (by 44.7%) for homosexual route. Moreover, the proportion of patients aged < 30 years increased considerably over the 12-year study period, while there was a decrease in the proportion of patients aged ≥ 35 years. The frequency of homosexual transmission increased by 86% from before 2011 to 2016, but the frequency of heterosexual transmission decreased by 49%. The frequency of transmission through intravenous drug use decreased in men and patients aged 25-29 years. For those infected through homosexual transmission, there was a significant increase in the numbers of patients aged 20-24 years and 25-29 years. It is important for developing countries to effectively prevent and control the transmission of HIV/AIDS; in particular, it is crucial to promote disease education and sexual protection among young men.