Cullen, P. F. | bioRxiv Science

bioRxiv2024

Protective Effects of Lipoxin A4 and B4 Signaling on the Inner Retina in a Mouse Model of Experimental Glaucoma

Glaucoma is a common neurodegenerative disease characterized by progressive degeneration of retinal ganglion cells (RGCs) and the retinal nerve fiber layer (RNFL), resulting in a gradual decline of vision. A recent study by our groups indicated that the levels of lipoxins A4 (LXA4) and B4 (LXB4) in the retina and optic nerve decrease following acute injury, and that restoring their function is neuroprotective. Lipoxins are members of the specialized pro-resolving mediator (SPM) family and play key roles to mitigate and resolve chronic inflammation and tissue damage. Yet, knowledge about lipoxin neuroprotective activity remains limited. Here we investigate the in vivo efficacy of exogenous LXA4 and LXB4 administration on the inner retina in a mouse model of chronic experimental glaucoma. To investigate the contribution of LXA4 signaling we used transgenic knockout (KO) mice lacking the two mouse LXA4 receptors (Fpr2/Fpr3-/-). Functional and structural changes of inner retinal neurons were assessed longitudinally using electroretinogram (ERG) and optical coherence tomography (OCT). At the end of the experiment, retinal samples were harvested for immunohistological assessment. While both lipoxins generated protective trends, only LXB4 treatment was significant, and consistently more efficacious than LXA4 in all endpoints. Both lipoxins also appeared to dramatically reduce Muller glial reactivity following injury. In comparison, Fpr2/Fpr3 deletion significantly worsened inner retinal injury and function, consistent with an essential protective role for endogenous LXA4. Together, these results support further exploration of lipoxin signaling as a treatment for glaucomatous neurodegeneration.

neuroscience↗

bioRxiv2021

CellMap: Characterizing the types and composition of iPSC-derived cells from RNA-seq data

Induced pluripotent stem cell (iPSC) derived cell types are increasingly employed as in vitro model systems for drug discovery. For these studies to be meaningful, it is important to understand the reproducibility of the iPSC-derived cultures and their similarity to equivalent endogenous cell types. Single-cell and single-nucleus RNA sequencing (RNA-seq) are useful to gain such understanding, but they are expensive and time consuming, while bulk RNA-seq data can be generated quicker and at lower cost. In silico cell type decomposition is an efficient, inexpensive, and convenient alternative that can leverage bulk RNA-seq to derive more fine-grained information about these cultures. We developed CellMap, a computational tool that derives cell type profiles from publicly available single-cell and single-nucleus datasets to infer cell types in bulk RNA-seq data from iPSC-derived cell lines.

bioinformatics↗