Enhanced retinal responses in Huntington’s disease patients

Pearl, Jocelynn; Heath, Laura M; Bergey, Dani E; Kelly, John P.; Smith, Corrie O.; Laurino, Mercy; Weiss, Avery H.; Price, Nathan D.; Laspada, Albert R; Bird, Thomas D.; Jayadev, Suman

doi:10.3233/jhd-170255

Cited by 14 publications

(9 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is because GEE can account for the correlation structure that results from repeated measurements of the same individual, leading to more consistent estimation of differences when compared to parametric tests that neglect correlation [46]. Others have used GEE to assess differences over time in human retinal ERG outputs, which are similar in nature to ABR progressions [47,48]. Of course, this method is only valid when thresholds are not statistically different, as we had found for the 32 kHz frequency (Fig 2).…”

Section: Discussionmentioning

confidence: 99%

SIRT3 promotes auditory function in young adult FVB/nJ mice but is dispensable for hearing recovery after noise exposure

et al. 2020

View full text Add to dashboard Cite

Noise-induced hearing loss (NIHL) affects millions of people worldwide and presents a large social and personal burden. Pharmacological activation of SIRT3, a regulator of the mitochondrial oxidative stress response, has a protective effect on hearing thresholds after traumatic noise damage in mice. In contrast, the role of endogenously activated SIRT3 in hearing recovery has not been established. Here we tested the hypothesis that SIRT3 is required in mice for recovery of auditory thresholds after a noise exposure that confers a temporary threshold shift (TTS). SIRT3-specific immunoreactivity is present in outer hair cells, around the post-synaptic regions of inner hair cells, and faintly within inner hair cells. Prior to noise exposure, homozygous Sirt3-KO mice have slightly but significantly higher thresholds than their wild-type littermates measured by the auditory brainstem response (ABR), but not by distortion product otoacoustic emissions (DPOAE). Moreover, homozygous Sirt3-KO mice display a significant reduction in the progression of their peak 1 amplitude at higher frequencies prior to noise exposure. After exposure to a single sub-traumatic noise dose that does not permanently reduce cochlear function, compromise cell survival, or damage synaptic structures in wild-type mice, there was no difference in hearing function between the two genotypes, measured by ABR and DPOAE. The numbers of hair cells and auditory synapses were similar in both genotypes before and after noise exposure. These loss-of-function studies complement previously published gain-of-function studies and help refine our understanding of SIRT3's role in cochlear homeostasis under different damage paradigms. They suggest that SIRT3 may promote spiral ganglion neuron function. They imply that cellular mechanisms of homeostasis, in addition to the mitochondrial oxidative stress response, act to restore hearing after TTS. Finally, we present a novel application of a biomedical statistical analysis for identifying changes between peak 1 amplitude progressions in ABR waveforms after damage.

show abstract

Section: Discussionmentioning

confidence: 99%

SIRT3 promotes auditory function in young adult FVB/nJ mice but is dispensable for hearing recovery after noise exposure

et al. 2020

View full text Add to dashboard Cite

show abstract

“…We have created a list of several neurodegenerative diseases (Table 4.1) that collectively affect a considerable proportion of the population, and in which retinal alterations have been demonstrated. Preliminary studies suggest that several other conditions not included here, including Huntington´s disease, stroke, and psychiatric disorders, have manifestations in the retina 3,[11][12][13][14] . The fact that these alterations are common to so many neurodegenerative conditions underscores the need for further studies to better understand the impact of CNS neurodegeneration on the retina.…”

Section: Retinal Alterations In Neurodegenerative Conditions Of the Bmentioning

confidence: 91%

CHAPTER 4. CNS Targets for the Treatment of Retinal Dystrophies: A Win–Win Strategy

Rosa¹,

Hernández‐Sánchez²

2018

Drug Discovery

View full text Add to dashboard Cite

As an extension of the central nervous system (CNS), the retina shares with the brain certain developmental, physiological, and pathological characteristics. However, the underlying mechanisms and pathological signs common to neurodegenerative conditions of both the retina and brain have been relatively overlooked. In animal models and in human patients, marked retinal alterations have been demonstrated in Alzheimer´s disease, Parkinson´s disease, and multiple sclerosis, among other pathologies. Furthermore, neurodegeneration of the retina and brain appears to be mediated by similar mechanisms, which include protein aggregation, neuroinflammation, and cell death. Analysis of the retina, which is easily accessible to objective techniques, may therefore constitute an effective tool for the screening and follow-up of CNS neurodegeneration. Moreover, patients with retinal neurodegeneration could potentially benefit from the broad array of pharmacological compounds that have been designed and tested for the treatment of the aforementioned CNS pathologies. Supporting this view, we have shown that GSK-3 inhibitors, which have already been tested in clinical trials to treat several neurodegenerative conditions of the brain, attenuate retinal damage and vision loss in a mouse model of retinitis pigmentosa. Furthermore, systemic proinsulin treatment preserves visual and cognitive function in mouse models of retinitis pigmentosa and precocious aging, respectively.

show abstract

“…Although Knapp et al [18] report findings from a single case study, it is of note that reduced ERG amplitudes are in keeping with results from mouse models of Huntington's Disease [19]. Moreover, a key difference between the two studies is that whereas Knapp et al [18] report data from an unmedicated premanifest subject, Pearl et al [17] report data from a group of HD-manifest patients. Some medications prescribed to HD patients, such as haloperidol have been shown to enhance ERG amplitudes in non-human primates, causing them to appear normal [20].…”

Section: The Retinamentioning

confidence: 96%

“…More recently, two studies have examined the possible effects of HD on the retina using electroretinograms (ERGs). Pearl et al [17] 1 Eye movement dysfunction is beyond the scope of this review and is comprehensively reviewed elsewhere [12,13,14] reported increased ERG amplitudes across a range flash intensities but there no differences in their latency. Conversely, Knapp et al [18] reported reduced ERG amplitudes in single case study of a 25 year old asymptomatic gene carrier with no differences in latencies.…”

Section: The Retinamentioning

confidence: 99%

Visual Dysfunction in Huntington’s Disease: A Systematic Review

Dhalla

Pallikadavath

Hutchinson

2019

JHD

View full text Add to dashboard Cite

It is well-documented that patients with Huntington's Disease exhibit specific deficits in visual cognition. A less well-documented literature also exists that suggests people with Huntington's Disease experience a number of disease-related changes to more rudimentary sensory visual processing. Here, we review evidence for the effects of Huntington's Disease on the integrity of the early visual pathways in humans along with changes to low-level visual sensitivity. We find evidence for reduced structural and functional integrity of the visual pathways, marked by retinal thinning, reduced VEP amplitude, and cell loss and thinning in visual cortex. We also find evidence of visual perceptual deficits, particularly for colour and motion. We suggest that future studies with well-defined HD and HD-related groups in appropriate numbers that systematically examine the relationship between structural changes to the visual system, basic visual perceptual deficits and disease stage/severity are therefore likely to yield promising results.

show abstract

Enhanced retinal responses in Huntington’s disease patients

Cited by 14 publications

References 30 publications

SIRT3 promotes auditory function in young adult FVB/nJ mice but is dispensable for hearing recovery after noise exposure

SIRT3 promotes auditory function in young adult FVB/nJ mice but is dispensable for hearing recovery after noise exposure

CHAPTER 4. CNS Targets for the Treatment of Retinal Dystrophies: A Win–Win Strategy

Visual Dysfunction in Huntington’s Disease: A Systematic Review

Contact Info

Product

Resources

About