Diurnal Photoreceptor Outer Segment Renewal in Mice Is Independent of Galectin-3

Esposito, Nicholas J.; Mazzoni, Francesca; Vargas, Jade; Finnemann, Silvia C.

doi:10.1167/iovs.62.2.7

Cited by 10 publications

(16 citation statements)

References 36 publications

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“…Our findings highlighted the existence of sexual dimorphism in the activity of the retina under basal conditions and following social stress, which is in contrast with previous studies in C57BL/6 mice (Mazzoni et al, 2019). This divergence may be explained by experimental considerations such as differences in the sample size and the statistical approaches used in both studies.…”

Section: Discussioncontrasting

confidence: 89%

Sex-Specific Retinal Anomalies Induced by Chronic Social Defeat Stress in Mice

Arsenault

Lavigne

Mansouri

et al. 2021

Front. Behav. Neurosci.

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Major depressive disorder (MDD) is one of the most common consequences of chronic stress. Still, there is currently no reliable biomarker to detect individuals at risk to develop the disease. Recently, the retina emerged as an effective way to investigate psychiatric disorders using the electroretinogram (ERG). In this study, cone and rod ERGs were performed in male and female C57BL/6 mice before and after chronic social defeat stress (CSDS). Mice were then divided as susceptible or resilient to stress. Our results suggest that CSDS reduces the amplitude of both oscillatory potentials and a-waves in the rods of resilient but not susceptible males. Similar effects were revealed following the analysis of the cone b-waves, which were faster after CSDS in resilient mice specifically. In females, rod ERGs revealed age-related changes with no change in cone ERGs. Finally, our analysis suggests that baseline ERG can predict with an efficacy up to 71% the expression of susceptibility and resilience before stress exposition in males and females. Overall, our findings suggest that retinal activity is a valid biomarker of stress response that could potentially serve as a tool to predict whether males and females will become susceptible or resilient when facing CSDS.

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Section: Discussioncontrasting

confidence: 89%

Sex-Specific Retinal Anomalies Induced by Chronic Social Defeat Stress in Mice

Arsenault

Lavigne

Mansouri

et al. 2021

Front. Behav. Neurosci.

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“…In more recent studies, we mostly sampled POS phagosomes immunolabeled with rhodopsin antibody B6-30, the same antibody used by Lewis and colleagues. However, our morning tissue collection time points were not exactly the same as the time points sampled by the other two recent studies and, again, did not include ZT 13.5 [ 23 , 40 ]. Therefore, it is currently unclear whether the evening peak observed by Lewis and colleagues is present in 129T2/SvEmsJ mice due to differences in sampling times and methodologies employed.…”

Section: An Intriguing Evening Peak In Rod Pos Rpe Phagocytosis In Micementioning

confidence: 99%

Probing Photoreceptor Outer Segment Phagocytosis by the RPE In Vivo: Models and Methodologies

Vargas

Finnemann

2022

IJMS

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In the vertebrate retina, the light-sensitive photoreceptor rods and cones constantly undergo renewal by generating new portions of the outer segment and shedding their distal, spent tips. The neighboring RPE provides the critical function of engulfing the spent material by phagocytosis. RPE phagocytosis of shed rod outer segment fragments is a circadian process that occurs in a burst of activity shortly after daily light onset with low activity at other times, a rhythm that has been reported for many species and over 50 years. In this review, we compare studies on the rhythm and quantity of RPE phagocytosis using different in vivo model systems and assessment methods. We discuss how measurement methodology impacts the observation and analysis of RPE phagocytosis. Published studies on RPE phagocytosis investigating mice further suggest that differences in genetic background and housing conditions may affect results. Altogether, a comparison between RPE phagocytosis studies performed using differing methodology and strains of the same species is not as straightforward as previously thought.

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“…Thus, the data presented are the means of the numbers of phagosomes per complete retina section. Our strategy for quantifying POS phagocytosis is one of a number of generally accepted methods and is employed by a number of groups who study mechanisms of RPE‐mediated POS phagocytosis 17,18,25‐30 . The representative images (Figure 1B) are blurry due to fluorescence emitted from the specimen outside the focal plane 31 .…”

Section: Methodsmentioning

confidence: 99%

“…Our strategy for quantifying POS phagocytosis is one of a number of generally accepted methods and is employed by a number of groups who study mechanisms of RPE-mediated POS phagocytosis. 17,18,[25][26][27][28][29][30] The representative images (Figure 1B) are blurry due to fluorescence emitted from the specimen outside the focal plane. 31 They contain oversaturation of the Rho-4D2 stained OS layer to visualize the relatively faint Rho-4D2 stained phagosomes in the RPE cell layer.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Core circadian clock genes Per1 and Per2 regulate the rhythm in photoreceptor outer segment phagocytosis

et al. 2021

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Retinal photoreceptors undergo daily renewal of their distal outer segments, a process indispensable for maintaining retinal health. Photoreceptor outer segment (POS) phagocytosis occurs as a daily peak, roughly about 1 hour after light onset. However, the underlying cellular and molecular mechanisms which initiate this process are still unknown. Here we show that, under constant darkness, mice deficient for core circadian clock genes (Per1 and Per2) lack a daily peak in POS phagocytosis. By qPCR analysis, we found that core clock genes were rhythmic over 24 hours in both WT and Per1, Per2 double mutant whole retinas. More precise transcriptomics analysis of laser capture microdissected WT photoreceptors revealed no differentially expressed genes between time points preceding and during the peak of POS phagocytosis. In contrast, we found that microdissected WT retinal pigment epithelium (RPE) had a number of genes that were differentially expressed at the peak phagocytic time point compared to adjacent ones. We also found a number of differentially expressed genes in Per1, Per2 double mutant RPE compared to WT ones at the peak phagocytic time point. Finally, based on STRING analysis, we found a group of interacting genes that potentially drive POS phagocytosis in the RPE. This potential pathway consists of genes such as: Pacsin1, Syp, Camk2b, and Camk2d among others. Our findings indicate that Per1 and Per2 are necessary clock components for driving POS phagocytosis and suggest that this process is transcriptionally driven by the RPE.

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Diurnal Photoreceptor Outer Segment Renewal in Mice Is Independent of Galectin-3

Cited by 10 publications

References 36 publications

Sex-Specific Retinal Anomalies Induced by Chronic Social Defeat Stress in Mice

Sex-Specific Retinal Anomalies Induced by Chronic Social Defeat Stress in Mice

Probing Photoreceptor Outer Segment Phagocytosis by the RPE In Vivo: Models and Methodologies

Core circadian clock genes Per1 and Per2 regulate the rhythm in photoreceptor outer segment phagocytosis

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