Blinded by the Light

Mudry, Maria Cristina De Vera; Kronenberg, Sven; Komatsu, Shun-ichiro; Aguirre, Gustavo D.

doi:10.1177/0192623312469308

Cited by 46 publications

(24 citation statements)

References 39 publications

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“…Light-induced damage of photoreceptors/RPE is dependent on several physical parameters including wavelength, intensity, duration of exposure, as well as biological factors such as animal species/strain, age, gender, degree of ocular pigmentation, body temperature, time of the circadian cycle, dark adaptation, and the contribution of specific mutations or genetic modifiers [for review see (46)]. This diversity complicates the comparison of light sensitivities between animal models as studies frequently involve the use of different light damage paradigms.…”

Section: Discussionmentioning

confidence: 99%

Assessment of visual function and retinal structure following acute light exposure in the light sensitive T4R rhodopsin mutant dog

Iwabe

Ying

Aguirre

et al. 2016

Experimental Eye Research

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The effect of acute exposure to various intensities of white light on visual behavior and retinal structure was evaluated in the T4R RHO dog, a naturally-occurring model of autosomal dominant retinitis pigmentosa due to a mutation in the Rhodopsin gene. A total of 14 dogs (ages: 4–5.5 months) were used in this study: 3 homozygous mutant RHOT4R/T4R, 8 heterozygous mutant RHOT4R/+, and 3 normal wild-type (WT) dogs. Following overnight dark adaptation, the left eyes were acutely exposed to bright white light with a monocular Ganzfeld dome, while the contralateral right eye was shielded. Each of the 3 homozygous (RHOT4R/T4R) mutant dogs had a single unilateral light exposure (LE) to a different (low, moderate, and high) dose of white light (corneal irradiance/illuminance: 0.1 mW/cm2, 170 lux; 0.5 mW/cm2, 820 lux; or 1 mW/cm2, 1590 lux) for 1min. All 8 heterozygous (RHOT4R/+) mutant dogs were exposed once to the same moderate dose of light. The 3 WT dogs had their left eyes exposed 1, 2, or 3 times to the same highest dose of light. Visual function prior to LE and at 2 weeks and 33 weeks after exposure was objectively assessed in the RHOT4R/T4R and WT dogs by using an obstacle-avoidance course. Transit time through the obstacle course was measured under different scotopic to photopic ambient illuminations. Morphological retinal changes were evaluated by non-invasive in vivo cSLO/sdOCT imaging and histology before and at several time-points (2–36 weeks) after light exposure. The analysis of the transit time through the obstacle course showed that no differences were observed in any of mutant or WT dogs at 2 weeks and 33 weeks post LE. The RHOT4R/T4R retina exposed to the lowest dose of white light showed no obvious changes in ONL thickness at 2 weeks, but mild decrease was noted 36 weeks after LE. The RHOT4R/T4R retina that received a moderate dose (showed an obvious decrease in ONL thickness along the superior and temporal meridians at 2 weeks post LE with more severe damage at 36 weeks post LE in all four meridians. The RHOT4R/T4R retina exposed to the high dose showed at 2 weeks after LE extensive ONL damage in all four meridians. This light intensity did not cause any retinal damage in WT dogs even after repeated (up to 3) LE. Analysis of ONL thickness in heterozygous mutant dogs exposed to the moderate dose of light confirmed the increased sensitivity to light damage of the superior/tapetal retina, and the occurrence of an ongoing cell death process several weeks after the acute LE. In conclusion, a short single exposure to a dose of white light that is not retinotoxic in WT dogs causes in the T4R RHO retina an acute loss of ONL in the central to mid peripheral region that keeps progressing over the course of several weeks. However, this severe retinal damage does not affect visual behavior presumably because of islands of surviving photoreceptors found in the area centralis including the newly discovered canine fovea-like area, and the lack of damage to peripheral photoreceptors.

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Section: Discussionmentioning

confidence: 99%

Assessment of visual function and retinal structure following acute light exposure in the light sensitive T4R rhodopsin mutant dog

Iwabe

Ying

Aguirre

et al. 2016

Experimental Eye Research

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“…To determine whether the retinal degeneration is light-related or not, it is essential to evaluate the topography of the retinal lesions (De Vera Mudry et al 2013). At least in the early stages of light-related retinal degeneration, the superior temporal retina, including the region around the optic disc, is more severely damaged along the vertical median of the eye (Tanito et al 2008, Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…The severity of peripheral retinal degeneration was evaluated using the same three-point grading scale as described above (Figure 4). Due to the significant overlap of the criteria for the minimal retinal degeneration described by De Vera Mudry et al, (2013), with the normal retinas in the 2 year old albino rats, we chose not to use the minimal grade in this study.…”

Section: Methodsmentioning

confidence: 99%

“…Spontaneously occurring retinal degeneration of uncertain etiology has also been reported in laboratory rats and mice (DiLoreto et al 1994). However, spontaneous retinal degeneration seen in the vehicle control group in long-term studies (≥ 6 months) in albino rodents is considered to be light-related, although an age effect cannot be excluded (Rao 1991; Perez and Perentes 1994; De Vera Mudry et al 2013). …”

Section: Introductionmentioning

confidence: 99%

“…A critical component of any study that aims to investigate the cause of retinal degeneration includes the morphologic topography of the retinal damage (De Vera Mudry et al 2013). In general, direct retinal damage by compounds tends to cause diffuse rather than more locally extensive retinal damage in the eye.…”

Section: Introductionmentioning

confidence: 99%

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Chemical Exacerbation of Light-induced Retinal Degeneration in F344/N Rats in National Toxicology Program Rodent Bioassays

et al. 2016

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Retinal degeneration due to chronic ambient light exposure is a common spontaneous age-related finding in albino rats, but it can also be related to exposures associated with environmental chemicals and drugs. Typically, light induced retinal degeneration has a central/hemispherical localization where as chemical induced retinal degeneration has a diffuse localization. This study was conducted to identify National Toxicology Program (NTP) rodent bioassays with treatment-related retinal degeneration, and to characterize the retinal lesions related to these retinal toxicities. A total of 3 chronic bioassays in F344/N rats were identified that had treatment-related increases in retinal degeneration (kava kava extract, acrylamide, and leucomalachite green). A retrospective light-microscopic evaluation of the retinas from rats in these three studies showed a dose-related increase in the frequencies of retinal degeneration, beginning with the loss of photoreceptor cells, followed by the inner nuclear layer cells. These dose-related increased frequencies of degenerative retinal lesions localized within the central/hemispherical region are suggestive of exacerbation of light-induced retinal degeneration.

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The laboratory mouse

Pritchett‐Corning,

Garner

2024

The UFAW Handbook on the Care and Management of Laboratory and Other Research Animals

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Blinded by the Light

Cited by 46 publications

References 39 publications

Assessment of visual function and retinal structure following acute light exposure in the light sensitive T4R rhodopsin mutant dog

Assessment of visual function and retinal structure following acute light exposure in the light sensitive T4R rhodopsin mutant dog

Chemical Exacerbation of Light-induced Retinal Degeneration in F344/N Rats in National Toxicology Program Rodent Bioassays

The laboratory mouse

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