Poor eyesight reveals a new vision gene

Biswas, Tathagata; Krishnan, Jaya; Rohner, Nicolas

doi:10.7554/elife.81520

Cited by 2 publications

(1 citation statement)

References 10 publications

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“…SERPINE3 is a functionally uncharacterized member of the large family of SERPIN protease inhibitors [ 74 , 75 ]. Recently the Serpine3 gene was found to be preferentially lost in species that do not rely on vision, suggesting that Serpine3 is essential for the development or maintenance of visual function [ 76 , 77 ]. However, there is a lack of available antibodies to mouse SERPINE3 protein, and we were unable to obtain conclusive evidence of SERPINE3 protein upregulation in the RPE after RD (Supplemental Data Figure S4 ).…”

Section: Discussionmentioning

confidence: 99%

The mouse retinal pigment epithelium mounts an innate immune defense response following retinal detachment

Abcouwer,

Miglioranza Scavuzzi,

Kish

et al. 2024

J Neuroinflammation

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The retinal pigment epithelium (RPE) maintains photoreceptor viability and function, completes the visual cycle, and forms the outer blood-retinal barrier (oBRB). Loss of RPE function gives rise to several monogenic retinal dystrophies and contributes to age-related macular degeneration. Retinal detachment (RD) causes separation of the neurosensory retina from the underlying RPE, disrupting the functional and metabolic relationships between these layers. Although the retinal response to RD is highly studied, little is known about how the RPE responds to loss of this interaction. RNA sequencing (RNA-Seq) was used to compare normal and detached RPE in the C57BL6/J mouse. The naïve mouse RPE transcriptome was compared to previously published RPE signature gene lists and from the union of these 14 genes (Bmp4, Crim1, Degs1, Gja1, Itgav, Mfap3l, Pdpn, Ptgds, Rbp1, Rnf13, Rpe65, Slc4a2, Sulf1 and Ttr) representing a core signature gene set applicable across rodent and human RPE was derived. Gene ontology enrichment analysis (GOEA) of the mouse RPE transcriptome identified expected RPE features and functions, such as pigmentation, phagocytosis, lysosomal and proteasomal degradation of proteins, and barrier function. Differentially expressed genes (DEG) at 1 and 7 days post retinal detachment (dprd) were defined as mRNA with a significant (padj≤0.05) fold change (FC) of 0.67 ≥ FC ≥ 1.5 in detached versus naïve RPE. The RPE transcriptome exhibited dramatic changes at 1 dprd, with 2297 DEG identified. The KEGG pathways and biological process GO groups related to innate immune responses were significantly enriched. Lipocalin 2 (Lcn2) and several chemokines were upregulated, while numerous genes related to RPE functions, such as pigment synthesis, visual cycle, phagocytosis, and tight junctions were downregulated at 1 dprd. The response was largely transient, with only 18 significant DEG identified at 7 dprd, including upregulation of complement gene C4b. Validation studies confirmed RNA-Seq results. Thus, the RPE quickly downregulates cell-specific functions and mounts an innate immune defense response following RD. Our data demonstrate that the RPE contributes to the inflammatory response to RD and may play a role in attraction of immune cells to the subretinal space.

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