Photoreceptor Cells With Profound Structural Deficits Can Support Useful Vision in Mice

Thompson, Stewart; Blodi, Frederick R.; Lee, Swan; Welder, Chris R.; Mullins, Robert F.; Tucker, Budd A.; Stasheff, Steven F.; Stone, Edwin M.

doi:10.1167/iovs.13-13661

Cited by 15 publications

(26 citation statements)

References 116 publications

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“…A flash ERG response has been used to assess the visual function of animal models of retinal degeneration for years (Jiang and Hamasaki, 1994;Pinilla et al, 2005;Lund et al, 2006;Sauve et al, 2006;Krohne et al, 2012;Thompson et al, 2014). ERGs are recorded using contact electrodes placed on the surface of the animal's corneas during fullfield light stimulation.…”

Section: Electroretinographymentioning

confidence: 99%

“…can also be conducted by invasive superior colliculus recording (Girman et al, 2003;Girman et al, 2005;Lund et al, 2006;Krohne et al, 2012;Thompson et al, 2014). The superior colliculus, located in the midbrain of mammals, receives direct retinal input that is topographically organized and corresponds to the areas of the retina that are stimulated by light (Siminoff et al, 1966) .…”

Section: Superior Colliculus Recording Evaluation Of the Animal's Abmentioning

confidence: 99%

“…Depending on the ability of the animal to discern a stationary image (based on retinal input to the dorsal lateral geniculate nucleus, superior colliculus, and/or pretectum), the animal may or may not be able to see the platform when the actual experiment is conducted (Prusky et al, 2000;Thompson et al, 2014). A running wheel test assesses vision by the enhancement or suppression of wheel-running activity.…”

Section: Superior Colliculus Recording Evaluation Of the Animal's Abmentioning

confidence: 99%

“…A running wheel test assesses vision by the enhancement or suppression of wheel-running activity. It has been used to determine the lowest luminance that supports useful vision for the mobility of a mouse model (Thompson et al, 2008;Thompson et al, 2014). The pupil light reflex (PLR), or constriction of the pupil of the eye in response to light, involves the integrity of the reflex loop involving midbrain centers (Klassen and Lund, 1990;MacLaren et al, 2006).…”

Section: Superior Colliculus Recording Evaluation Of the Animal's Abmentioning

confidence: 99%

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Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Nazari

Zhang

Zhu

et al. 2015

Progress in Retinal and Eye Research

177

142

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Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. AMD is classified as either neovascular (NV-AMD) or non-neovascular (NNV-AMD). Cumulative damage to the retinal pigment epithelium, Bruch's membrane, and choriocapillaris leads to dysfunction and loss of RPE cells. This causes degeneration of the overlying photoreceptors and consequential vision loss in advanced NNV-AMD (Geographic Atrophy). In NV-AMD, abnormal growth of capillaries under the retina and RPE, which leads to hemorrhage and fluid leakage, is the main cause of photoreceptor damage. Although a number of drugs (e.g., anti-VEGF) are in use for NV-AMD, there is currently no treatment for advanced NNV-AMD. However, replacing dead or dysfunctional RPE with healthy RPE has been shown to rescue dying photoreceptors and improve vision in animal models of retinal degeneration and possibly in AMD patients. Differentiation of RPE from human embryonic stem cells (hESC-RPE) and from induced pluripotent stem cells (iPSC-RPE) has created a potentially unlimited source for replacing dead or dying RPE. Such cells have been shown to incorporate into the degenerating retina and result in anatomic and functional improvement. However, major ethical, regulatory, safety, and technical challenges have yet to be overcome before stem cell-based therapies can be used in standard treatments. This review outlines the current knowledge surrounding the application of hESC-RPE and iPSC-RPE in AMD. Following an introduction on the pathogenesis and available treatments of AMD, methods to generate stem cell-derived RPE, immune reaction against such cells, and approaches to deliver desired cells into the eye will be explored along with broader issues of efficacy and safety. Lastly, strategies to improve these stem cell-based treatments will be discussed.

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Section: Electroretinographymentioning

confidence: 99%

Section: Superior Colliculus Recording Evaluation Of the Animal's Abmentioning

confidence: 99%

Section: Superior Colliculus Recording Evaluation Of the Animal's Abmentioning

confidence: 99%

Section: Superior Colliculus Recording Evaluation Of the Animal's Abmentioning

confidence: 99%

See 2 more Smart Citations

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Nazari

Zhang

Zhu

et al. 2015

Progress in Retinal and Eye Research

177

142

View full text Add to dashboard Cite

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“…26 Dark-adapted retinas from the left eye, directly exposed to blast, (4 retinas for each time point) were positioned with the ganglion cell layer (GCL) down onto a multielectrode array with 10-lm contacts spaced 200-lm apart (Multichannel Systems, Reutlingen, Germany). The array was mounted on a microscope (Axioplan; Zeiss, Gottingen, Germany) and perfused with 378C oxygenated Ringer medium at 2.5 to 4 mL/min (in mM: 124 NaCl, 2.5 KCl, 2 CaCl 2 , 2 MgCl 2 , 1.25 NaH 2 PO 4 , 26 NaHCO 3 , and 22 glucose).…”

Section: Multi-electrode Array Analysis Of Single Rgc Physiologymentioning

confidence: 99%

Early Detection of Subclinical Visual Damage After Blast-Mediated TBI Enables Prevention of Chronic Visual Deficit by Treatment With P7C3-S243

Dutca

Stasheff

Hedberg-Buenz

et al. 2014

Investigative Ophthalmology & Visual Science

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Provocative PERG testing serves as a noninvasive test in the living organism to identify early damage to the visual system, which may reflect corresponding damage in the brain that is not otherwise detectable by noninvasive means. This provides the basis for developing an earlier diagnostic test to identify patients at risk for developing chronic CNS and visual system damage after TBI at an earlier stage when treatments may be more effective in preventing these sequelae. In addition, treatment with the neuroprotective agent P7C3-S243 after TBI protects from visual system dysfunction after TBI.

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Psychophysical testing in rodent models of glaucomatous optic neuropathy

Grillo

Koulen

2015

Experimental Eye Research

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Processing of visual information begins in the retina, with photoreceptors converting light stimuli into neural signals. Ultimately, signals are transmitted to the brain through signaling networks formed by interneurons, namely bipolar, horizontal and amacrine cells providing input to retinal ganglion cells (RGCs), which form the optic nerve with their axons. As part of the chronic nature of glaucomatous optic neuropathy, the increasing and irreversible damage and ultimately loss of neurons, RGCs in particular, occurs following progressive damage to the optic nerve head (ONH), eventually resulting in visual impairment and visual field loss. There are two behavioral assays that are typically used to assess visual deficits in glaucoma rodent models, the visual water task and the optokinetic drum. The visual water task can assess an animal’s ability to distinguish grating patterns that are associated with an escape from water. The optokinetic drum relies on the optomotor response, a reflex turning of the head and neck in the direction of the visual stimuli, which usually consists of rotating black and white gratings. This reflex is a physiological response critical for keeping the image stable on the retina. Driven initially by the neuronal input from direction-selective RGCs, this reflex is comprised of a number of critical sensory and motor elements. In the presence of repeatable and defined stimuli, this reflex is extremely well suited to analyze subtle changes in the circuitry and performance of retinal neurons. Increasing the cycles of these alternating gratings per degree, or gradually reducing the contrast of the visual stimuli, threshold levels can be determined at which the animal is no longer tracking the stimuli, and thereby visual function of the animal can be determined non-invasively. Integrating these assays into an array of outcome measures that determine multiple aspects of visual function is a central goal in vision research and can be realized, for example, by the combination of measuring optomotor reflex function with electroretinograms (ERGs) and optical coherence tomography (OCT) of the retina. These structure-function correlations in vivo are urgently needed to identify disease mechanisms as potential new targets for drug development. Such a combination of the experimental assessment of the optokinetic reflex (OKN) or optomotor reflex (OMR) with other measures of retinal structure and function is especially valuable for research on GON. The chronic progression of the disease is characterized by a gradual decrease in function accompanied by a concomitant increase in structural damage to the retina, therefore the assessment of subtle changes is key to determining the success of novel intervention strategies.

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Photoreceptor Cells With Profound Structural Deficits Can Support Useful Vision in Mice

Abstract: Photoreceptors that lack fully formed outer segments can support useful vision. This challenges the idea that normal cellular structure needs to be completely reproduced for transplanted cells to contribute to useful vision.

Cited by 15 publications

References 116 publications

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Early Detection of Subclinical Visual Damage After Blast-Mediated TBI Enables Prevention of Chronic Visual Deficit by Treatment With P7C3-S243

Psychophysical testing in rodent models of glaucomatous optic neuropathy

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