| First Author | Palko SI | Year | 2024 |
| Journal | Glia | Volume | 72 |
| Issue | 6 | Pages | 1067-1081 |
| PubMed ID | 38497356 | Mgi Jnum | J:348220 |
| Mgi Id | MGI:7624565 | Doi | 10.1002/glia.24514 |
| Citation | Palko SI, et al. (2024) ER-stress response in retinal Muller glia occurs significantly earlier than amyloid pathology in the Alzheimer's mouse brain and retina. Glia 72(6):1067-1081 |
| abstractText | Alzheimer's 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 Muller 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 Muller glia, confirmed by immunohistochemical characterization. Further unbiased transcriptomic assays of the P30 NLGF retina revealed that retinal Muller glia were the most sensitive responding cells in this mouse retina, compared with 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 Abeta likely facilitated UPR. Altogether, these findings suggest that Muller glia act as a sentinel for AD pathology in the retina and should aid for both intervention and diagnosis. |
