Human Photoreceptor Outer Segments Shorten During Light Adaptation

Abstract

PURPOSE. Best disease is a macular dystrophy caused by mutations in the BEST1 gene. Affected individuals exhibit a reduced electro-oculographic (EOG) response to changes in light exposure and have significantly longer outer segments (OS) than age-matched controls. The purpose of this study was to investigate the anatomical changes in the outer retina during dark and light adaptation in unaffected and Best disease subjects, and to compare these changes to the EOG.METHODS. Unaffected (n ¼ 11) and Best disease patients (n ¼ 7) were imaged at approximately 4-minute intervals during an approximately 40-minute dark-light cycle using spectral domain optical coherence tomography (SD-OCT). EOGs of two subjects were obtained under the same conditions. Automated three-dimensional (3-D) segmentation allowed measurement of light-related changes in the distances between five retinal surfaces.RESULTS. In normal subjects, there was a significant decrease in outer segment equivalent length (OSEL) of À2.14 lm (95% confidence interval [CI], À1.77 to À2.51 lm) 10 to 20 minutes after the start of light adaptation, while Best disease subjects exhibited a significant increase in OSEL of 2.07 lm (95% CI, 1.79-2.36 lm). The time course of the change in OS length corresponded to that of the EOG waveform. CONCLUSIONS.Our results strongly suggest that the light peak phase of the EOG is temporally related to a decreased OSEL in normal subjects, and the lack of a light peak phase in Best disease subjects is associated with an increase in OSEL. One potential role of Bestrophin-1 is to trigger an increase in the standing potential that approximates the OS to the apical surface of the RPE to facilitate phagocytosis.

Impact of Bleaching on Photoreceptors in Different Intermediate AMD Phenotypes

“…Furthermore, similar to vitelliform lesions, RPD were demonstrated to be composed of lipofuscin-like material representing unphagocytized photoreceptor OS, which may be interpreted as an indirect sign of RPE dysfunction 12. In addition, in similarity to our findings in RPD eyes, Abràmoff et al28 have recently demonstrated that eyes with Best disease, which is known to be caused by RPE impairment, are characterized by a longstanding photoreceptor OS enlargement following light exposure.…”

Impact of Bleaching on Photoreceptors in Different Intermediate AMD Phenotypes

“…Furthermore, similar to vitelliform lesions, RPD were demonstrated to be composed of lipofuscin-like material representing unphagocytized photoreceptor OS, which may be interpreted as an indirect sign of RPE dysfunction 12. In addition, in similarity to our findings in RPD eyes, Abràmoff et al28 have recently demonstrated that eyes with Best disease, which is known to be caused by RPE impairment, are characterized by a longstanding photoreceptor OS enlargement following light exposure.…”

Polarization optical coherence tomography optoretinography: verifying light-induced photoreceptor outer segment shrinkage and subretinal space expansion

“…Light-induced shrinkage of photoreceptors OSEL reported in healthy human subjects was observed after 10 to 20 min of continuous light exposure in dark-adapted retinas. This study, 15 using a commercial OCT system, reported a mean shrinkage of , which is significantly higher than the parallel-polarization shrinkage observed in our study. This discrepancy is predominantly due to different definitions of the OS length.…”

Light-Induced Thickening of Photoreceptor Outer Segment Layer Detected by Ultra-High Resolution OCT Imaging

“…A decrease of approximately 2 μm in OSEL length after 10 to 20 minutes' light adaptation was reported in normal subjects. 13 These observations on the human fovea are opposite to what we observed in the mouse eye. However, it should be noted that while the photoreceptors OS length shrank, the RPE thickness was increased.…”

Impact of Bleaching on Photoreceptors in Different Intermediate AMD Phenotypes

“…Furthermore, similar to vitelliform lesions, RPD were demonstrated to be composed of lipofuscin-like material representing unphagocytized photoreceptor OS, which may be interpreted as an indirect sign of RPE dysfunction 12. In addition, in similarity to our findings in RPD eyes, Abràmoff et al28 have recently demonstrated that eyes with Best disease, which is known to be caused by RPE impairment, are characterized by a longstanding photoreceptor OS enlargement following light exposure.…”

Polarization optical coherence tomography optoretinography: verifying light-induced photoreceptor outer segment shrinkage and subretinal space expansion

“…Light-induced shrinkage of photoreceptors OSEL reported in healthy human subjects was observed after 10 to 20 min of continuous light exposure in dark-adapted retinas. This study, 15 using a commercial OCT system, reported a mean shrinkage of , which is significantly higher than the parallel-polarization shrinkage observed in our study. This discrepancy is predominantly due to different definitions of the OS length.…”

Light-Induced Thickening of Photoreceptor Outer Segment Layer Detected by Ultra-High Resolution OCT Imaging

“…A decrease of approximately 2 μm in OSEL length after 10 to 20 minutes' light adaptation was reported in normal subjects. 13 These observations on the human fovea are opposite to what we observed in the mouse eye. However, it should be noted that while the photoreceptors OS length shrank, the RPE thickness was increased.…”

Impact of Bleaching on Photoreceptors in Different Intermediate AMD Phenotypes

“…Furthermore, similar to vitelliform lesions, RPD were demonstrated to be composed of lipofuscin-like material representing unphagocytized photoreceptor OS, which may be interpreted as an indirect sign of RPE dysfunction 12. In addition, in similarity to our findings in RPD eyes, Abràmoff et al28 have recently demonstrated that eyes with Best disease, which is known to be caused by RPE impairment, are characterized by a longstanding photoreceptor OS enlargement following light exposure.…”

Polarization optical coherence tomography optoretinography: verifying light-induced photoreceptor outer segment shrinkage and subretinal space expansion

“…Light-induced shrinkage of photoreceptors OSEL reported in healthy human subjects was observed after 10 to 20 min of continuous light exposure in dark-adapted retinas. This study, 15 using a commercial OCT system, reported a mean shrinkage of , which is significantly higher than the parallel-polarization shrinkage observed in our study. This discrepancy is predominantly due to different definitions of the OS length.…”

Light-Induced Thickening of Photoreceptor Outer Segment Layer Detected by Ultra-High Resolution OCT Imaging

“…A decrease of approximately 2 μm in OSEL length after 10 to 20 minutes' light adaptation was reported in normal subjects. 13 These observations on the human fovea are opposite to what we observed in the mouse eye. However, it should be noted that while the photoreceptors OS length shrank, the RPE thickness was increased.…”