| First Author | Zuo H | Year | 2024 |
| Journal | Exp Eye Res | Volume | 244 |
| Pages | 109935 | PubMed ID | 38763352 |
| Mgi Jnum | J:360868 | Mgi Id | MGI:7645021 |
| Doi | 10.1016/j.exer.2024.109935 | Citation | Zuo H, et al. (2024) Prohibitin 2 deficiency in photoreceptors leads to progressive retinal degeneration and facilitated Muller glia engulfing microglia debris. Exp Eye Res 244:109935 |
| abstractText | Muller glia and microglia are capable of phagocytosing fragments of retinal cells in response to retinal injury or degeneration. However, the direct evidence for their mutual interactions between Muller glia and microglia in the progression of retinal degeneration (RD) remains largely unclear. This study aims to construct a progressive RD mouse model and investigate the activated pattern of Muller glia and the interplay between Muller glia and microglia in the early stage or progression of RD. A Prohibitin 2 (Phb2) photoreceptor-specific knockout (RKO) mouse model was generated by crossing Phb2(flox/flox) mice with Rhodopsin-Cre mice. Optical Coherence Tomography (OCT), histological staining, and Electroretinography (ERG) assessed retinal structure and function, and RKO mice exhibited progressive RD from six weeks of age. In detail, six-week-old RKO mice showed no significant retinal impairment, but severe vision dysfunction and retina thinning were shown in ten-week-old RKO mice. Furthermore, RKO mice were sensitive to Light Damage (LD) and showed severe RD at an early age after light exposure. Bulk retina RNA-seq analysis from six-week-old control (Ctrl) and RKO mice showed reactive retinal glia in RKO mice. The activated pattern of Muller glia and the interplay between Muller glia and microglia was visualized by immunohistology and 3D reconstruction. In six-week-old RKO mice or light-exposed Ctrl mice, Muller glia were initially activated at the edge of the retina. Moreover, in ten-week-old RKO mice or light-exposed six-week-old RKO mice with severe photoreceptor degeneration, abundant Muller glia were activated across the whole retinas. With the progression of RD, phagocytosis of microglia debris by activated Muller glia were remarkably increased. Altogether, our study establishes a Phb2 photoreceptor-specific knockout mouse model, which is a novel mouse model of RD and can well demonstrate the phenotype of progressive RD. We also report that Muller glia in the peripheral retina is more sensitive to the early damage of photoreceptors. Our study provides more direct evidence for Muller glia engulfing microglia debris in the progression of RD due to photoreceptor Phb2 deficiency. |
