Retinal Oxygenation and Oxygen Metabolism in Abyssinian Cats with a Hereditary Retinal Degeneration

Padnick‐Silver, Lissa; Derwent, J. J. Kang; Giuliano, Elizabeth A.; Narfström, Kristina; Linsenmeier, Robert A.

doi:10.1167/iovs.05-1284

Cited by 80 publications

(71 citation statements)

References 23 publications

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“…The hyperactivity also is not simply due to a difference in background strain because similar hyperactivity (albeit developing with a slower time course) occurred in ganglion cells of the additional control strain (rd1/C57). It might be hypothesized that the hyperactivity results from increased pO 2 in the face of decreasing oxygen consumption by rod photoreceptors, but inner retinal oxygenation is normal in cats with retinal degeneration (Padnick-Silver et al 2006). Instead the increase in ganglion cell activity suggests a significant alteration either in intrinsic ganglion cell electrophysiological properties or in the organization of the neural circuitry presynaptic to the ganglion cells.…”

Section: Increased Spontaneous Activity In Rd1 Ganglion Cellsmentioning

confidence: 99%

Emergence of Sustained Spontaneous Hyperactivity and Temporary Preservation of off Responses in Ganglion Cells of the Retinal Degeneration (rd1) Mouse

Stasheff¹

2008

Journal of Neurophysiology

218

286

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Stasheff SF. Emergence of sustained spontaneous hyperactivity and temporary preservation of OFF responses in ganglion cells of the retinal degeneration (rd1) mouse. J Neurophysiol 99: 1408 -1421, 2008. First published January 23, 2008 doi:10.1152/jn.00144.2007. Complex alterations in the anatomy of outer retinal pathways accompany photoreceptor degeneration in the rd1 mouse model of retinitis pigmentosa, whereas inner retinal neurons appear relatively preserved. However, the progressive loss of photoreceptor input likely alters the neural circuitry of the inner retina. This study investigated resulting changes in the activity of surviving ganglion cells. Multielectrode recording monitored spontaneous and light-evoked extracellular action potentials simultaneously from 30 to 90 retinal ganglion cells of wild-type (wt) or rd1 mice. In rd1 mice, this activity evolves through three phases. First, normal spontaneous "waves" of correlated firing are seen at postnatal day 7 (P7) and last until shortly after eye opening. Second, at P14, full-field light flashes evoke reliable responses in many cells, with preferential preservation of OFF responses. These diminish as photoreceptor degeneration progresses. Third, once light-evoked responses have disappeared in early adulthood, surviving rd1 ganglion cells fire at a much higher spontaneous frequency than normal, sometimes in rhythmic bursts that are distinct from the developmental "waves." This hyperactivity is sustained well into adulthood, for weeks after photoreceptors have disappeared. Thus striking alterations occur in inner retinal physiology as retinal degeneration progresses in the rd1 mouse. Blindness occurs in the face of sustained hyperactivity among ganglion cells, which remain viable for months despite this activity. ON and OFF responses are differentially affected in early stages of degeneration. While the source of these changes remains to be learned, such features should be considered in designing more effective treatments for these disorders.

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Section: Increased Spontaneous Activity In Rd1 Ganglion Cellsmentioning

confidence: 99%

Emergence of Sustained Spontaneous Hyperactivity and Temporary Preservation of off Responses in Ganglion Cells of the Retinal Degeneration (rd1) Mouse

Stasheff¹

2008

Journal of Neurophysiology

218

286

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“…Following an initial loss of photoreceptors, the oxygen demand in the outer retina is significantly decreased, resulting in an increase in outer retinal oxygen concentrations (Padnick-Silver et al, 2006;Stone et al, 1999;Yu et al, 2000Yu et al, , 2004. These oxygen levels are maintained due to the inability of the choroid to autoregulate in response to increased outer retinal oxygen concentrations (Stone et al, 1999;Yu et al, 2004;Yu and Cringle, 2005).…”

Section: Introductionmentioning

confidence: 99%

Mathematical models of retinitis pigmentosa: The oxygen toxicity hypothesis

Roberts

Gaffney

Luthert

et al. 2017

Journal of Theoretical Biology

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The group of genetically mediated diseases, known collectively as retinitis pigmentosa (RP), cause retinal degeneration and, hence, loss of vision. The most common inherited retinal degeneration, RP is currently untreatable. The retina detects light using cells known as photoreceptors, of which there are two types: rods and cones. In RP, genetic mutations cause patches of photoreceptors to degenerate and typically directly affect either rods or cones, but not both. During disease progression, degenerate patches spread and the unaffected photoreceptor type also begins to degenerate. The cause underlying these phenomena is currently unknown.The oxygen toxicity hypothesis proposes that secondary photoreceptor loss is due to hyperoxia (toxically high oxygen levels), which results from the decrease in oxygen uptake following the initial loss of photoreceptors. In this paper, we construct mathematical models, formulated as 1D systems of partial differential equations, to investigate this hypothesis. Using a combination of numerical simulations, asymptotic analysis and travelling wave analysis, we find that degeneration may spread due to hyperoxia, and generate spatiotemporal patterns of degeneration similar to those seen in vivo. We determine the conditions under which a degenerate patch will spread and show that the wave speed of degeneration is a monotone decreasing function of the local photoreceptor density. Lastly, the effects of treatment with antioxidants and trophic factors, and of capillary loss, upon the dynamics of photoreceptor loss and recovery are considered.

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“…Affected cats show characteristics similar to those in a human form of retinitis pigmentosa, and, thus, Abyssinian cats have become a useful research model for future treatment modalities in humans with retinal degeneration [91,[96][97][98][99][100][101] . During recent years, procedures for feline neuroretinal transplantation have been developed with the aim of restoring some function or rescuing degenerating photoreceptors in this Abyssinian cat mutant [90] .…”

Section: Catsmentioning

confidence: 99%

Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals – Part I: Animal Models and Toxicity Assays

et al. 2010

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Aims: Experimental retinal research has gained great importance due to the ophthalmic pharmacotherapy era. An increasing number of drugs are constantly released into the market for the treatment of retinal diseases. In this review, animal species, animal models and toxicity assays in retinal research are discussed. Methods: An extensive search of the literature was performed to review various aspects of the methods of investigation of drug toxicity. The different types of animal species, as well as single animal models available for the evaluation of safety and efficacy of retinal pharmacotherapy, were identified. In addition, a large variety of reported laboratory techniques were critically examined. Results: In vitro studies are the first-line experiments for the development of a new drug for retinal diseases, using retinal pigment epithelial cells and other cell lines. The next step involves in vivo animal studies where nonhuman primates are considered the gold standard. However, cost and legal issues make their use difficult. Mice and rats provide genetically controlled models for investigations. Pigs, dogs and cats represent good large-size animal models, while rabbits are one of the most used species for retinal toxicity evaluations. Various laboratory methods were identified, including light microscopy, electron microscopy, electroretinography and new emerging methods, such as optical coherence tomography and scanning laser ophthalmoscopy for experimental purposes. Conclusions: A great number of animal species and models are available that simulate retinal diseases and provide experimental data for further human use. Work with animal models should include properly designed toxicity assays to obtain reliable results for safety and efficacy.

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Retinal Oxygenation and Oxygen Metabolism in Abyssinian Cats with a Hereditary Retinal Degeneration

Cited by 80 publications

References 23 publications

Emergence of Sustained Spontaneous Hyperactivity and Temporary Preservation of off Responses in Ganglion Cells of the Retinal Degeneration (rd1) Mouse

Emergence of Sustained Spontaneous Hyperactivity and Temporary Preservation of off Responses in Ganglion Cells of the Retinal Degeneration (rd1) Mouse

Mathematical models of retinitis pigmentosa: The oxygen toxicity hypothesis

Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals – Part I: Animal Models and Toxicity Assays

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