Optical Coherence Tomography: Imaging Mouse Retinal Ganglion Cells &lt;em&gt;In Vivo&lt;/em&gt;

Jagodzinska, Jolanta; Sarzi, Emmanuelle; Cavalier, Mélanie; Seveno, Marie; Baecker, Volker; Hamel, Christian; Péquignot, Marie O.; Delettre, Cécile

doi:10.3791/55865

Cited by 8 publications

(4 citation statements)

References 13 publications

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“…Results shown here concern the sum of the thicknesses of Retinal Nerve Fiber Layer (RNFL, that contains RGC axons) plus Ganglion Cell Layer (GCL, that contains RGC bodies). The measurement of RNFL/GCL complex in the mouse is preferable to the measurement of RNFL alone that is usually too thin to be correctly quantified ( Jagodzinska et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Topical nerve growth factor prevents neurodegenerative and vascular stages of diabetic retinopathy

et al. 2022

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Specific and effective preventive treatment for diabetic retinopathy (DR) is presently unavailable, mostly because the early stages of the complication have been, until recently, poorly understood. The recent demonstration that the vascular phase of DR is preceded and possibly caused by the neurodegeneration of retinal ganglion cells suggests that DR could, at least theoretically, be prevented through an early neuroprotective approach. The aims of our study were to clarify the natural history of diabetes-driven retinal neurodegeneration and to verify the possibility to prevent DR using topical nerve growth factor (NGF). The results of the study show that retinal neurodegeneration, characterized by the loss of retinal ganglion cells represents a relatively early phenomenon of diabetes (between 5 and 16 weeks of age), which tends to be self-limiting in the long run. Neurodegeneration is followed by the development of DR-related vascular dysfunctions, as confirmed by the development of acellular capillaries and the loss of retinal pericytes. Both retinal neurodegeneration and subsequent vascular dysfunction can be successfully prevented by topical NGF administration. These findings suggest that: 1) The first stage of DR consists in a self-limiting retinal neurodegeneration 2) The demonstrated effectiveness of topical NGF in the prevention of DR could be rapidly translated into clinical practice.

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Section: Methodsmentioning

confidence: 99%

Topical nerve growth factor prevents neurodegenerative and vascular stages of diabetic retinopathy

et al. 2022

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“…Mice were anesthetized (Ketamine at 20 mg/ml and Xylazine at 1.17 162 mg/ml) and their pupils dilated with 10% phenylephrine and 0.5% tropicamide provided as eye drops (Systane Ultra, Alcon). OCT was performed for mouse retinas with the spectral domain (SD) ophthalmic imaging system as described previously (Jagodzinska et al, 2017 ). Thickness of retinal layers was measured manually with ImageJ image processing program (National Institute of Health) at 0.3 mm distance from the optic nerve.…”

Section: Methodsmentioning

confidence: 99%

Early Retinal Defects in Fmr1−/y Mice: Toward a Critical Role of Visual Dys-Sensitivity in the Fragile X Syndrome Phenotype?

Perche

Felgerolle

Ardourel

et al. 2018

Front. Cell. Neurosci.

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Fragile X Syndrome (FXS) is caused by a deficiency in Fragile X Mental Retardation Protein (FMRP) leading to global sensorial abnormalities, among which visual defects represent a critical part. These visual defects are associated with cerebral neuron immaturity especially in the primary visual cortex. However, we recently demonstrated that retinas of adult Fmr1−/y mice, the FXS murine model, present molecular, cellular and functional alterations. However, no data are currently available on the evolution pattern of such defects. As retinal stimulation through Eye Opening (EO) is a crucial signal for the cerebral visual system maturation, we questioned the precocity of molecular and functional retinal phenotype. To answer this question, we studied the retinal molecular phenotype of Fmr1−/y mice before EO until adult age and the consequences of the retinal loss of Fmrp on retinal function in young and adult mice. We showed that retinal molecular defects are present before EO and remain stable at adult age, leading to electrophysiological impairments without any underlying structural changes. We underlined that loss of Fmrp leads to a wide range of defects in the retina, settled even before EO. Our work demonstrates a critical role of the sensorial dysfunction in the Fmr1−/y mice overall phenotype, and provides evidence that altered peripheral perception is a component of the sensory processing defect in FXS conditions.

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“…Prior to the OCT procedure, mice were anesthetized by intraperitoneal injection using a ketamine/xylazine mixture as described above, and their pupils were dilated with 1% tropicamide ophthalmic drops. The mice were then placed in the animal imaging mount-rodent alignment stage (AIM-RAS) setup for image acquisition ( 29 ). Axis manipulation before image capture was done to centrally align the optic nerve head (ONH) in the middle of the scans as a landmark.…”

Section: Methodsmentioning

confidence: 99%

The dose-response relationship of subretinal gene therapy with rAAV2tYF-CB-hRS1 in a mouse model of X-linked retinoschisis

Hassan,

Hsu,

Thompson

et al. 2024

Front. Med.

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PurposeX-linked retinoschisis (XLRS), due to loss-of-function mutations in the retinoschisin (RS1) gene, is characterized by a modest to severe decrease in visual acuity. Clinical trials for XLRS utilizing intravitreal (IVT) gene therapy showed ocular inflammation. We conducted a subretinal dose–response preclinical study using rAAV2tYF-CB-hRS1 utilizing the Rs1 knockout (Rs1-KO) mouse to investigate short- and long-term retinal rescue after subretinal gene delivery.MethodsRs1-KO mice were subretinally injected with 2 μL of rAAV2tYF-CB-hRS1 vector with 8E9 viral genomes (vg)/eye, 8E8 vg/eye, 8E7 vg/eye, or sham injection, and compared to untreated eyes. Reconstitution of human RS1 protein was detected using western blotting. Analysis of retinal function by electroretinography (ERG) and structural analysis by optical coherence tomography (OCT) were performed at 1, 2, 3, 5, 7, and 12 months post injection (MPI). Immunohistochemistry (IHC) was performed to evaluate cone rescue on the cellular level. Functional vision was evaluated using a visually guided swim assay (VGSA).ResultsWestern blotting analysis showed human RS1 protein expression in a dose-dependent manner. Quantification of western blotting showed that the RS1 protein expression in mice treated with the 8E8 vg dose was near the wild-type (WT) expression levels. ERG demonstrated dose-dependent effects: At 1 MPI the 8E8 vg dose treated eyes had higher light-adapted (LA) ERG amplitudes in 3.0 flash and 5 Hz flicker compared to untreated (p < 0.0001) and sham-treated eyes (p < 0.0001) which persisted until the 12 MPI endpoint, consistent with improved cone function. ERG b-wave amplitudes were higher in response to dark-adapted (DA) 0.01 dim flash and 3.0 standard combined response (SCR) compared to sham-treated (p < 0.01) and untreated eyes (p < 0.001) which persisted until 3 MPI, suggesting short-term improvement of the rod photoreceptors. All injections, including sham-treated, resulted in a cyst severity score of 1 (no cavities), with significant reductions compared to untreated eyes up to 3 MPI (p < 0.05). The high and low dose groups showed inconsistent ERG improvements, despite reduced cyst severity, emphasizing the dose-dependent nature of gene augmentation’s efficacy and the tenuous connection between cyst reduction and ERG improvement. IHC data showed a significant cone rescue in eyes treated with the 8E8 vg dose compared to sham-treated and untreated eyes. VGSA showed better functional vision in 8E8 vg dose treated mice. Eyes treated with the highest dose showed occasional localized degeneration in the outer nuclear layer.ConclusionOur data suggest that a dose of 8E8 vg/eye subretinally improves retinal function and structure in the Rs1-KO mouse. It improves cone function, rod function, and reduces cyst severity. Sham treatment resolves schisis cysts, but 8E8 vg/eye is needed for optimal retinal electrical function rescue. These findings offer a promising path for clinical translation to human trials.

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Optical Coherence Tomography: Imaging Mouse Retinal Ganglion Cells <em>In Vivo</em>

Cited by 8 publications

References 13 publications

Topical nerve growth factor prevents neurodegenerative and vascular stages of diabetic retinopathy

Topical nerve growth factor prevents neurodegenerative and vascular stages of diabetic retinopathy

Early Retinal Defects in Fmr1−/y Mice: Toward a Critical Role of Visual Dys-Sensitivity in the Fragile X Syndrome Phenotype?

The dose-response relationship of subretinal gene therapy with rAAV2tYF-CB-hRS1 in a mouse model of X-linked retinoschisis

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