| Experiment Id | GSE254524 | Name | ER-stress response in retinal Mller glia occurs significantly earlier than amyloid pathology in in the Alzheimers mouse brain and retina |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2025-01-23 |
| description | Alzheimers Disease (AD) pathogenesis is thought to begin up to 20 years before cognitive symptoms appear, suggesting the need for more sensitive diagnostic biomarkers of AD. In this report, we demonstrated pathological changes in retinal Mller glia significantly earlier than amyloid pathology in AD mouse models. By utilizing the knock-in NLGF mouse model, we surprisingly discovered an increase in reticulon 3 (RTN3) protein levels in the NLGF retina as early as postnatal day 30 (P30). Despite RTN3 being a canonically neuronal protein, this increase was noted in the retinal Mller glia, confirmed by immunohistochemical characterization. Further unbiased transcriptomic assays of the P30 NLGF retina revealed that retinal Mller glia were the most sensitive responding cells in this mouse retina, compared to other cell types including photoreceptor cells and ganglion neurons. Pathway analyses of differentially expressed genes in glia cells showed activation of ER stress response via the upregulation of unfolded protein response (UPR) proteins such as ATF4 and CHOP. Early elevation of RTN3 in response to challenges by toxic A likely facilitated UPR. Altogether, these findings suggest that Mller glia act as a sentinel for AD pathology in the retina and should aid for both intervention and diagnosis. Retinas from two wildtype and two nlgf mice were dissected at P30. Cells were isolated into a single-cell suspension and processed using the 10x genomics single-cell RNA sequencing pipeline. |
