Mouse Models of Achromatopsia in Addressing Temporal “Point of No Return” in Gene-Therapy

Achromatopsia is characterized by amblyopia, photophobia, nystagmus, and color blindness. Previous animal models of achromatopsia have shown promising results using gene augmentation to restore cone function. However, the optimal therapeutic window to elicit recovery remains unknown. Here, we attempted two rounds of gene augmentation to generate recoverable mouse models of achromatopsia including a Cnga3 model with a knock-in stop cassette in intron 5 using Easi-CRISPR (Efficient additions with ssDNA inserts-CRISPR) and targeted embryonic stem (ES) cells. This model demonstrated that only 20% of CNGA3 levels in homozygotes derived from target ES cells remained, as compared to normal CNGA3 levels. Despite the low percentage of remaining protein, the knock-in mouse model continued to generate normal cone phototransduction. Our results showed that a small amount of normal CNGA3 protein is sufficient to form “functional” CNG channels and achieve physiological demand for proper cone phototransduction. Thus, it can be concluded that mutating the Cnga3 locus to disrupt the functional tetrameric CNG channels may ultimately require more potent STOP cassettes to generate a reversible achromatopsia mouse model. Our data also possess implications for future CNGA3-associated achromatopsia clinical trials, whereby restoration of only 20% functional CNGA3 protein may be sufficient to form functional CNG channels and thus rescue cone response.

Correlation Between Electroretinogram and Visual Prognosis in Metallic Intraocular Foreign Body Injury

Purpose: This study aims to investigate the correlation between electroretinogram (ERG) and visual outcome in eyes with metallic intraocular foreign body (IOFB) injury.Methods: Cases with metallic IOFB injuries with preoperative ERG from January 2008 to May 2020 were reviewed retrospectively. Five ERG responses were recorded, including rod response, maximal response, oscillatory potentials, cone response, and 30-Hz flicker. The results were compared between the affected and the contralateral eyes. All patients received surgery to remove IOFBs. The correlation between amplitudes, implicit times, and grades of ERG with final best-corrected visual acuity (BCVA) was analyzed.Results: A total of 33 eyes of 33 patients were included. The eyes with IOFB had generally delayed implicit time and reduced amplitude in all waves. The maximum change was found in oscillatory potentials S3 and N1 (0.42 ± 0.42 and 1.95 ± 1.97 of the fellow eyes, respectively, p < 0.05). All amplitudes were negatively correlated with the final BCVA (rs: −0.676 to −0.459, all p < 0.05). In contrast, all implicit times were positively correlated with final BCVA, although, some of them were not statistically significant (rs: 0.035 to 0.687). Among them, oscillatory potential P3 has the highest correlation coefficient (rs = 0.687, p < 0.001). All grades of ERG waves were statistically correlated with the final BCVA (rs: −0.596 to −0.664, all p < 0.001).Conclusions: ERG can be used to assess visual outcome in metallic IOFB injury after surgery. Oscillatory potentials provided the most significant responses.

Carbon-phosphide monolayer with high carrier mobility and perceptible I–V response for superior gas sensing

We introduce the first-principle theoretical calculations to understand the adsorption mechanism of different gas molecules on monolayered carbon phosphide with semi-metallic electrical conductivity and graphene-like Dirac cone response.

Electroretinography in eight species of neotropical deer

ABSTRACT The aim of this study was to establish normal baseline ERG values of 23 anesthetized deer belonging to 8 neotropical species (Mazama americana, Mazama nemorivaga, Mazama gouazoubira, Mazama nana, Mazama bororo, Ozotocerus bezoarticus, Odocoileus virginianus and Blastocerus dichotomus). Only right eyes were studied. Chemical restraint was performed using xylazine associated with ketamine, IM, for M. americana, M. gouazoubira, M. nemorivaga, M. nana, M. bororo, O. bezoarticus and O. virginianus. A combination of tiletamine/zolazepam diluted in xylazine 2% was used for B. dichotomus individuals. After 20min of dark adaptation, electroretinograms were obtained using a handheld electroretinography (ERG) machine using the QuickRetCheck Protocol at three different light intensities: 0.01cd.s/m2, 3cd.s/m2, and 10cd.s/m2. After light adaptation, photopic phase was recorded. A-wave amplitude recorded during pattern mixed rod/cone response in M. americana was significantly lower when compared to B. dichotomus. No other differences were observed between the species studied. ERG in Neotropical deer is applicable using a portable ERG system and did not show differences among species in relation to the retinal response at different light intensities. Therefore, the lifestyle of the species is more dictated by the selection pressure of the environment than by physiological factors.

A Novel Method of Color Appearance Simulation Using Achromatic Point Locus With Lightness Dependence

The purpose of the present study is to propose a simple algorithm for color appearance simulation under a color illuminant. Achromatic point is a chromaticity of rays that appear neither red nor green, neither blue nor yellow under a given illuminant condition. Saturation and hue of surface colors are evaluated with respect to the achromatic point of the same lightness, while the achromatic point under a colored illuminant depends on the lightness tested. We previously found that this achromatic point locus can be simply approximated as a line with a parallel offset from the lightness axis of CIE LAB space normalized to daylight. We propose a model that applies shifts in the lightness direction after applying hue/saturation shifts using the cone-response (von Kries) transformation under an iso-lightness constraint, such that achromatic points would be aligned with the lightness axis in the CIE LAB space under daylight normalization. We tested this algorithm, which incorporates evaluation of color appearance in different lightness levels, using #theDress image. Resemblance between our simulation and subjective color-matching results implies that human color vision possibly processes shifts in color and lightness independently, as a previous study reported. Changes in the chromaticity distribution of the images were compared with conventional models, and the proposed model preserved relative color difference better, especially at the lower lightness levels. The better performance in lower lightness levels would be advantageous in displays with wider dynamic range in luminance. This implies that the proposed model is effective in simulating color appearance of images with nonnegligible lightness and color differences.