Regenerative and restorative medicine for eye disease

Gelder, Russell N. Van; Chiang, Michael F.; Dyer, Michael A.; Greenwell, Thomas N.; Levin, Leonard A.; Wong, Rachel; Svendsen, Clive N.

doi:10.1038/s41591-022-01862-8

Cited by 52 publications

(27 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 Over the last two decades, numerous strategies have emerged, including gene replacement therapy, 2 gene editing approaches, 3 optogenetics, 4 retinal electrical implants, 5 induced pluripotent stem cell (iPSC)-derived retinal cell replacements, 6 and pharmacological agents. [7][8][9] These approaches can restore light-sensing ability at the retinal level and lead to improvements in visual perception in patients to varying extents. Studies of synthetic retinoid treatment in patients with RPE65 or LRAT mutations have led to improvements in visual field area and visual cortex activation, as seen on fMRI scans.…”

Section: Resultsmentioning

confidence: 99%

Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration

et al. 2022

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration

et al. 2022

View full text Add to dashboard Cite

“…The demonstration of measurable acuity from photoswitch-treated rd1 retinas suggests that the EyeCandy system may be used to estimate and compare the effects of vision restoration methodologies, such as stem cell photoreceptor replacement, 44 small molecule photoswitches, optogenetic gene therapy, 45 and opto-electronic stimulation 46 on potential acuity ex vivo. In the current work, we show proof of concept for the photoswitch BENAQ, 47 but several other photoswitches with varying cell targets in the retina remain to be tested.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Murine Retinal Acuity Ex Vivo Using Multielectrode Array Recordings

Babino

Benster

Laprell

et al. 2023

Trans. Vis. Sci. Tech.

Self Cite

View full text Add to dashboard Cite

Purpose Visual acuity, measured by resolution of optotypes on a standard eye chart, is a critical clinical test for function of the visual system in humans. Behavioral tests in animals can be used to estimate visual acuity. However, such tests may be limited in the study of mutants or after synthetic vision restoration techniques. Because the total response of the retina to a visual scene is encoded in spiking patterns of retinal ganglion cells, it should be possible to estimate visual acuity in vitro from the retina by analyzing retinal ganglion cell output in response to test stimuli. Methods We created a method, EyeCandy, that combines a visual stimulus-generating engine with analysis of multielectrode array retinal recordings via a machine learning approach to measure murine retinal acuity in vitro. Visual stimuli included static checkerboards, drifting gratings, and letter optotypes. Results In retinas from wild-type C57Bl/6 mice, retinal acuity measurement for a drifting grating was 0.4 cycles per degree. In contrast, retinas from adult rd1 mice with outer retinal degeneration showed no detectable acuity. A comparison of acuities among different regions of the retina revealed substantial variation, with the inferior–nasal quadrant having highest RA. Letter classification accuracy of a projected Early Treatment Diabetic Retinopathy eye chart reached 99% accuracy for logMAR 3.0 letters. EyeCandy measured a restored RA of 0.05 and 0.08 cycles per degree for static and dynamic stimuli respectively from the retina of the rd1 mouse treated with the azobenzene photoswitch BENAQ. Conclusions Machine learning may be used to estimate retinal acuity. Translational Relevance The use of ex vivo retinal acuity measurement may allow determination of effects of mutations, drugs, injury, or other manipulations on retinal visual function.

show abstract

“…The latter compound could then be subjected to an anion metathesis using a saturated aqueous solution of KPF 6 to afford BDHPPy + , PF 6 − (92%). The structures of these compounds were confirmed by 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy methods as well as mass spectrometry analyses (see the Experimental Section and the Supporting Information).…”

Section: Synthesesmentioning

confidence: 97%

“…Infrared spectra were recorded on a PerkinElmer Spectrum Two Fourier transform infrared spectrometer using attenuated total reflexion modes. 1 H NMR and 13 C NMR spectra were recorded on a Bruker Avance 500 or 400 MHz spectrometer in CDCl 3 or CD 3 CN. Chemical shifts are calibrated to residual solvent peaks.…”

Section: General Procedures and Instrumentationmentioning

confidence: 99%

All Visible Light Photoswitch Based on the Dimethyldihydropyrene Unit Operating in Aqueous Solutions with High Quantum Yields

Ziani

Cobo

Jouvenot

et al. 2022

JACS Au

View full text Add to dashboard Cite

Molecular systems and devices whose properties can be modulated using light as an external stimulus are the subject of numerous research studies in the fields of materials and life sciences. In this context, the use of photochromic compounds that reversibly switch upon light irradiation is particularly attractive. However, for many envisioned applications, and in particular for biological purposes, illumination with harmful UV light must be avoided and these photoactivable systems must operate in aqueous media. In this context, we have designed a benzo[e]-fused dimethyldihydropyrene compound bearing a methyl-pyridinium electroacceptor group that meets these requirements. This compound (closed state) is able to reversibly isomerize under aerobic conditions into its corresponding cyclophanediene form (open isomer) through the opening of its central carbon−carbon bond. Both the photo-opening and the reverse photoclosing processes are triggered by visible light illumination and proceed with high quantum yields (respectively 14.5% yield at λ = 680 nm and quantitative quantum yield at λ = 470 nm, in water). This system has been investigated by nuclear magnetic resonance and absorption spectroscopy, and the efficient photoswitching behavior was rationalized by spin-flip time-dependent density functional theory calculations. In addition, it is demonstrated that the isomerization from the open to the closed form can be electrocatalytically triggered.

show abstract

Regenerative and restorative medicine for eye disease

Cited by 52 publications

References 73 publications

Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration

Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration

Assessment of Murine Retinal Acuity Ex Vivo Using Multielectrode Array Recordings

All Visible Light Photoswitch Based on the Dimethyldihydropyrene Unit Operating in Aqueous Solutions with High Quantum Yields

Contact Info

Product

Resources

About