Wavelength of light and photophobia in inherited retinal dystrophy

Otsuka, Yuki; Oishi, Akio; Miyata, Manabu; Oishi, Maho; Hasegawa, Tomoko; Numa, Shogo; Ikeda, Hanako Ohashi; Tsujikawa, Akitaka

doi:10.1038/s41598-020-71707-2

Cited by 14 publications

(12 citation statements)

References 25 publications

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“…It is challenging to speculate how these findings translate into clinical settings, because of the lack of corresponding data from RP patients. Hypersensitivity to bright light (called by the debated misnomer “photophobia”) is common in RP ( Hamel, 2006 ; Otsuka et al, 2020 ), and could in part result from similar hyperexcitation of the primary visual tract as observed in RP model mice. The relatively well-maintained behavioral vision of Rho P23H/WT mice may also be reflected in clinical settings, as many RP patients show minimal disturbances in subjective vision even at an advanced disease stage ( Hartong et al, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

Visual System Hyperexcitability and Compromised V1 Receptive Field Properties in Early-Stage Retinitis Pigmentosa in Mice

Leinonen

Lyon²,

Palczewski³

et al. 2022

eNeuro

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Inherited retinal degenerative diseases are a prominent cause of blindness. Although mutations causing death of photoreceptors are mostly known, the pathophysiology downstream in the inner retina and along the visual pathway is incompletely characterized in the earliest disease stages. Here, we investigated retinal, midbrain and cortical visual function using electroretinography (ERG), the optomotor response (OMR), visual evoked potentials (VEPs), respectively, and single unit electrophysiology at the primary visual cortex (V1) in light-adapted juvenile (approximately one-month-old) and young adult (three-month-old) Rho P23H/WT mice, representative of early-stage retinitis pigmentosa (RP). Photopic ERG revealed up to ∼30% hypersensitivity to light in Rho P23H/WT mice, as measured by the light intensity required to generate half-maximal b-wave (I 50 parameter). Rho P23H/WT mice also showed increased OMRs toward low spatial frequency (SF) drifting gratings, indicative of visual overexcitation at the midbrain level. At the V1 level, VEPs and single-cell recordings revealed prominent hyperexcitability in the juvenile Rho P23H/WT mice. Mean VEP amplitudes for light ON stimuli were nearly doubled in one-month-old Rho P23H/WT mice compared with controls, and more than doubled for light OFF. Single-cell recordings showed a significantly increased spontaneous V1 neuron firing in the Rho P23H/WT mice, and persistent contrast and temporal sensitivities. In contrast, direction selectivity was severely compromised. Our data suggest that during early RP, the visual pathway becomes hyperexcited. This could have both compensatory and deleterious consequences for visual behavior. Further studies on the mechanisms of hyperexcitability are warranted as this could lead to therapeutic interventions for RP.

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Section: Discussionmentioning

confidence: 99%

Visual System Hyperexcitability and Compromised V1 Receptive Field Properties in Early-Stage Retinitis Pigmentosa in Mice

Leinonen

Lyon²,

Palczewski³

et al. 2022

eNeuro

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“…In addition, some patients (17%; 4/24) reported photophobia. This is a relatively frequent symptom in patients with IRDs and is thought to reflect an early involvement of photopigment-containing cells [15,22]. It is suggested that light hypersensitivity occurs due to impairment of either S-cones in the parafoveal region, rods, and/or photosensitive retinal ganglion cells, but the mechanism is not fully understood [22].…”

Section: Disease Onsetmentioning

confidence: 99%

“…This is a relatively frequent symptom in patients with IRDs and is thought to reflect an early involvement of photopigment-containing cells [15,22]. It is suggested that light hypersensitivity occurs due to impairment of either S-cones in the parafoveal region, rods, and/or photosensitive retinal ganglion cells, but the mechanism is not fully understood [22]. Interestingly, a subset of DRAM2 patients (12%; 3/24) described difficulty seeing in dark environments and dark adaption difficulties as their initial symptoms, suggesting an early rod impairment [14,16].…”

Section: Disease Onsetmentioning

confidence: 99%

The Clinical Spectrum and Disease Course of DRAM2 Retinopathy

Krašovec

Volk

Habjan

et al. 2022

IJMS

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Pathogenic variants in DNA-damage regulated autophagy modulator 2 gene (DRAM2) cause a rare autosomal recessive retinal dystrophy and its disease course is not well understood. We present two Slovenian patients harboring a novel DRAM2 variant and a detailed review of all 23 other patients described to date. Whole exome and whole genome sequencing were performed in the two patients, and both underwent ophthalmological examination with a 2-year follow-up. PubMed was searched for papers with clinical descriptions of DRAM2 retinopathy. Patient 1 was homozygous for a novel variant, p.Met1?, and presented with the acute onset of photopsia and retina-wide retinopathy at the age of 35 years. The patient was first thought to have an autoimmune retinopathy and was treated with mycophenolate mofetil, which provided some symptomatic relief. Patient 2 was compound heterozygous for p.Met1? and p.Leu246Pro and presented with late-onset maculopathy at the age of 59 years. On review, patients with DRAM2 retinopathy usually present in the third decade with central visual loss, outer retinal layer loss on optical coherence tomography and a hyperautofluorescent ring on fundus autofluorescence. Either cone–rod or rod–cone dystrophy phenotype is observed on electroretinography, reflecting the importance of DRAM2 in both photoreceptor types. Non-null variants can result in milder disease.

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“…Retinal imaging using visible light is often associated with considerable discomfort glare 31 , 32 . Photophobia increases with decreasing wavelength, and it was therefore expected that R-AF would be better tolerated 6 , 7 .…”

Section: Discussionmentioning

confidence: 99%

Fundus autofluorescence imaging using red excitation light

Birtel

Bauer

Pauleikhoff

et al. 2023

Sci Rep

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Retinal disease accounts significantly for visual impairment and blindness. An important role in the pathophysiology of retinal disease and aging is attributed to lipofuscin, a complex of fluorescent metabolites. Fundus autofluorescence (AF) imaging allows non-invasive mapping of lipofuscin and is a key technology to diagnose and monitor retinal disease. However, currently used short-wavelength (SW) excitation light has several limitations, including glare and discomfort during image acquisition, reduced image quality in case of lens opacities, limited visualization of the central retina, and potential retinal light toxicity. Here, we establish a novel imaging modality which uses red excitation light (R-AF) and overcomes these drawbacks. R-AF images are high-quality, high-contrast fundus images and image interpretation may build on clinical experience due to similar appearance of pathology as on SW-AF images. Additionally, R-AF images may uncover disease features that previously remained undetected. The R-AF signal increases with higher abundance of lipofuscin and does not depend on photopigment bleaching or on the amount of macular pigment. Improved patient comfort, limited effect of cataract on image quality, and lack of safety concerns qualify R-AF for routine clinical monitoring, e.g. for patients with age-related macular degeneration, Stargardt disease, or for quantitative analysis of AF signal intensity.

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Wavelength of light and photophobia in inherited retinal dystrophy

Cited by 14 publications

References 25 publications

Visual System Hyperexcitability and Compromised V1 Receptive Field Properties in Early-Stage Retinitis Pigmentosa in Mice

Visual System Hyperexcitability and Compromised V1 Receptive Field Properties in Early-Stage Retinitis Pigmentosa in Mice

The Clinical Spectrum and Disease Course of DRAM2 Retinopathy

Fundus autofluorescence imaging using red excitation light

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