Augustine, J. | Search bioRxiv

bioRxiv2024

Modulation of microglia activation after human donor retinal ganglion cell transplantation

Stem cell-derived retinal ganglion cell transplantation therapy offers a promising avenue for restoring vision in patients with significant retinal ganglion cell loss. The major challenge in this therapeutic approach is ensuring the survival of transplanted human donor retinal ganglion cells within the host retina. Here, we demonstrated the pivotal role of host retinal microglia and macrophages in the rejection, acceptance and survival of human donor cells. To identify the potential targets for treatment in microglia-retinal ganglion cell interaction, we assembled a single-cell atlas for mouse retina during development, aging, maturation and across neurodegenerative conditions. To our knowledge, this is the largest integrated atlas containing 1,053,629 cells including 36,080 myeloid cells. The downstream analysis highlighted phagocytosis among other known pathways involved in microglia activation, neuroinflammation and host retinal ganglion cell damage. We hypothesized that the same mechanisms are responsible for donor retinal ganglion cell removal. We showed that it is possible to improve the survival of human donor stem cell-derived retinal ganglion cells through modulation of the host retinal microglia. Pretreatment of human donor retinal ganglion cells with annexin V and/or soluble Fas ligand before transplantation led to a 2.5-fold increase in donor cell survival, including the outgrowth of axons targeting optic nerve head. Detailed analyses of the host mouse retina post-transplantation revealed morphological changes microglia and macrophages typical for activation in neuroinflammation. These findings indicate that soluble Fas ligand and annexin V treatment can be used to improve the success rate of transplantation of neurons within the retina and central nervous system.

cell biology↗

bioRxiv2023

A comparison of telencephalon composition among chickens, junglefowl, and wild galliforms.

Domestication is the process of modifying animals for human benefit through selective breeding in captivity. One of the traits that often diverges is the size of the brain and its constituent regions; almost all domesticated species have relatively smaller brains and brain regions than their wild ancestors. Although the effects of domestication on the brain have been investigated across a range of both mammal and bird species, almost nothing is known about the neuroanatomical effects of domestication on the worlds most common bird: the chicken (Gallus gallus). We compared the quantitative neuroanatomy of the telencephalon of white leghorn chickens with red junglefowl, their wild counterpart, and several wild galliform species. We focused specifically on the telencephalon because telencephalic regions typically exhibit the biggest differences in size in domesticate-wild comparisons. Relative telencephalon size was larger in chickens than in junglefowl and ruffed grouse (Bonasa umbellus). The relative size of telencephalic regions did not differ between chickens and junglefowl but did differ in comparison with ruffed grouse. Ruffed grouse had larger hyperpallia and smaller entopallial, nidopallial and striatal volumes than chickens and junglefowl. Multivariate analyses that included an additional three wild grouse species corroborated these findings: chicken and junglefowl have relatively larger nidopallial and striatal volumes than grouse. Conversely, the mesopallial and hyperpallial volumes tended to be relatively smaller in chickens and junglefowl. From this suite of comparisons, we conclude that chickens do not follow a pattern of widespread decreases in telencephalic region sizes that is often viewed as typical of domestication. Instead, chickens have undergone a mosaic of changes with some regions increasing and others decreasing in size and there are few differences between chickens and junglefowl.

neuroscience↗