The role of interferon regulatory factor 8 for retinal tissue homeostasis and development of choroidal neovascularisation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE182504 | GEO | 2021/08/27
REPOSITORIES: GEO
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Project description:Microglia are the tissue-resident macrophages of the retina and brain, being critically involved in organ development, tissue homeostasis, and response to cellular damage. Until now, little is known about the transcriptional profile of human retinal microglia and how they differentiate from peripheral monocytes, as well as from brain microglia. Additionally, the degree to which mice are suitable models for human retinal microglia is still not clear. The present study applies fluorescence-activated cell sorting to isolate human retinal microglia from enucleated eyes and compares their transcriptional profile with that of whole retinal tissue, as well as classical, intermediate and non-classical monocytes. In addition, human retinal microglia are compared to murine retinal microglia, isolated from at least two-years old Cx3cr1GFP/+ mice, as well as human brain microglia obtained from the literature. Several overexpressed genes were identified in retinal microglia when compared to whole retinal tissue, as well as classical, intermediate, and non-classical monocytes, among them IL1B, C2, C3, TREM2, P2RY12 and SPP1. In relation to whole retina sequencing, several risk genes, such as APOE and TGBR1, as well as PLXDC2 and ARHGAP22 associated with age-related macular degeneration (AMD) and diabetic retinopathy (DRP), were preferentially expressed in retinal microglia, indicating their potential pathophysiological involvement. The top expressed genes exhibited a strong consistency between retinal and brain microglia, among them CD74, SPP1, ACTB, FTL and C3. There was a high degree of similarity between human and murine retinal microglia, although there were several species-specific genes, revealing for which genes mice are suitable models for human retinal microglia. This study provides detailed insights into the molecular profile of human retinal microglia and indicate a high similarity to brain microglia. It advances our under-standing about their role in human retinal disease, such as AMD and DRP. The similarities and differences between human and mice will facilitate the transferability of knowledge between both species.
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2021-03-15 | GSE160845 | GEO
Project description:Cone photoreceptors are the primary initiator of visual transduction in the human retina. Dysfunction or death of rod photoreceptors precedes cone loss in many retinal and macular degenerative diseases, suggesting a rod-dependent trophic support for cone survival. Rod differentiation and homeostasis are dependent on the basic motif leucine zipper transcription factor NRL. The loss of Nrl in mice (Nrl-/-) results in a retina with predominantly S-opsin containing cones that exhibit molecular and functional characteristics of WT cones. Here we report that Nrl-/- retina undergoes a rapid but transient period of degeneration in early adulthood, with cone apoptosis, retinal detachment, alterations in retinal vessel structure, and activation and translocation of retinal microglia. However, cone degeneration stabilizes by four months of age, resulting in a thinned but intact outer nuclear layer with residual cones expressing S- and M-opsins and a preserved photopic ERG. At this stage, microglia translocate back to the inner retina and reacquire a quiescent morphology. Gene profiling analysis during the period of transient degeneration reveals misregulation of stress response and inflammation genes, implying their involvement in cone death. The Nrl-/- retina illustrates the long-term viability of cones in the absence of rods and may serve as a model for elucidating mechanisms of cone homeostasis and degeneration that would be relevant to understanding diseases of the cone-dominant human macula. Targets were generated from a pair of retinas (one Nrl-/- mouse) per biological replicate. Four biological replicates were generated for each of the five aging timepoints (1, 2, 4, 6, and 10 months post natal).
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