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Monitoring Visual Cortical Activities During Progressive Retinal Degeneration Using Functional Bioluminescence Imaging.

ABSTRACT: Mouse models of inherited retinal degenerative diseases such as retinitis pigmentosa are characterized by degeneration of photoreceptors, which hinders the generation of signal to be transmitted to the visual cortex. By monitoring Ca²⁺-bioluminescence neural activity, we quantified changes in visual cortical activities in response to visual stimuli in RD10 mice during progression of retinal degeneration, which correlated with progressive deteriorations of electro-retinography signal from the eyes. The number of active neurons in the visual cortex, the intensity of Ca²⁺-bioluminescence response, and neural activation parameter showed progressive deterioration during aging. Further, we correlated the thinning of retina as measured by Optical Coherence Tomography with the decrease in visual cortical activities as retinal degeneration progressed. The present study establishes Ca²⁺-bioluminescence monitoring as a longitudinal imaging modality to characterize activities in visual cortex of retinal degenerative disease models and therapeutic interventions.

SUBMITTER: Narcisse D

PROVIDER: S-EPMC8530108 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Monitoring Visual Cortical Activities During Progressive Retinal Degeneration Using Functional Bioluminescence Imaging.

Narcisse Darryl D Mustafi Sourajit M SM Carlson Michael M Kim Sanghoon S Batabyal Subrata S Wright Weldon W Mohanty Samarendra K SK

Frontiers in neuroscience 20211004

Mouse models of inherited retinal degenerative diseases such as retinitis pigmentosa are characterized by degeneration of photoreceptors, which hinders the generation of signal to be transmitted to the visual cortex. By monitoring Ca<sup>2+</sup>-bioluminescence neural activity, we quantified changes in visual cortical activities in response to visual stimuli in RD10 mice during progression of retinal degeneration, which correlated with progressive deteriorations of electro-retinography signal f ...[more]

PMID: 34690687

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Project description:BackgroundPlacental dysfunction underlies numerous complications of pregnancy. A major obstacle to understanding the roles of potential mediators of placental pathology has been the absence of suitable methods for tissue-specific gene manipulation and sensitive assays for studying gene functions in the placentas of intact animals. We describe a sensitive and noninvasive method of repetitively tracking placenta-specific gene expression throughout pregnancy using lentivirus-mediated transduction of optical reporter genes in mouse blastocysts.Methodology/principal findingsZona-free blastocysts were incubated with lentivirus expressing firefly luciferase (Fluc) and Tomato fluorescent fusion protein for trophectoderm-specific infection and transplanted into day 3 pseudopregnant recipients (GD3). Animals were examined for Fluc expression by live bioluminescence imaging (BLI) at different points during pregnancy, and the placentas were examined for tomato expression in different cell types on GD18. In another set of experiments, blastocysts with maximum photon fluxes in the range of 2.0E+4 to 6.0E+4 p/s/cm(2)/sr were transferred. Fluc expression was detectable in all surrogate dams by day 5 of pregnancy by live imaging, and the signal increased dramatically thereafter each day until GD12, reaching a peak at GD16 and maintaining that level through GD18. All of the placentas, but none of the fetuses, analyzed on GD18 by BLI showed different degrees of Fluc expression. However, only placentas of dams transferred with selected blastocysts showed uniform photon distribution with no significant variability of photon intensity among placentas of the same litter. Tomato expression in the placentas was limited to only trophoblast cell lineages.Conclusions/significanceThese results, for the first time, demonstrate the feasibility of selecting lentivirally-transduced blastocysts for uniform gene expression in all placentas of the same litter and early detection and quantitative analysis of gene expression throughout pregnancy by live BLI. This method may be useful for a wide range of applications involving trophoblast-specific gene manipulations in utero.

Project description:BackgroundElectrophysiological impairments in the magnocellular visual system have been reported among patients with schizophrenia, but previous theories proposed that these deficits may begin in the retina. We therefore sought to evaluate the potential contribution of the retina by comparing retinal and cortical visual electrophysiological impairments between patients with schizophrenia and healthy controls.MethodsWe recruited patients with schizophrenia and age- and sex-matched healthy controls. We recorded the P100 amplitude and latency using electroencephalography (EEG) while projecting low (0.5 cycles/degree) or high (15 cycles/degree) spatial frequency gratings at a temporal frequency of 0 Hz or 8 Hz. We compared the P100 results with previous results for retinal ganglion cell activity (N95) in these participants. We analyzed data using repeated-measures analysis of variance and correlation analyses.ResultsWe recruited 21 patients with schizophrenia and 29 age- and sex-matched healthy controls. Results showed decreased P100 amplitude and increased P100 latency among patients with schizophrenia compared with healthy controls (p < 0.05). Analyses reported the main effects of spatial and temporal frequency but no interaction effects of spatial or temporal frequency by group. Moreover, correlation analysis indicated a positive association between P100 latency and previous retinal results for N95 latency in the schizophrenia group (p < 0.05).DiscussionAlterations in the P100 wave among patients with schizophrenia are consistent with the deficits in early visual cortical processing shown in the literature. These deficits do not seem to correspond to an isolated magnocellular deficit but appear to be associated with previous retinal measurements. Such an association emphasizes the role of the retina in the occurrence of visual cortical abnormalities in schizophrenia. Studies with coupled electroretinography-EEG measurements are now required to further explore these findings.Clinical trials registrationhttps://clinicaltrials.gov/ct2/show/NCT02864680.

Dataset Information

Monitoring Visual Cortical Activities During Progressive Retinal Degeneration Using Functional Bioluminescence Imaging.

Publications

Monitoring Visual Cortical Activities During Progressive Retinal Degeneration Using Functional Bioluminescence Imaging.

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