Abstract
Purpose :
Degenerative eye diseases affect millions of people and can ultimately lead to blindness. Facilitating regeneration of retinal neurons in mammals could prevent vision loss. The spiny mouse, Acomys cahirinus, displays remarkable regenerative abilities in many tissues. We previously observed a significant increase in cell proliferation in response to retinal damage in Acomys as compared to the non-regenerator Mus musculus. Here, we tested the hypothesis that proliferating cells responding to retinal injury in Acomys are microglia and Müller glia, which are associated with suppression of reactive gliosis to promote regeneration.
Methods :
All procedures were performed in accordance with guidelines established by the ARVO Statement for the Use of Animals. Acute retinal damage was induced via intravitreal injection of NMDA. Retinal sections were prepared from adult Acomys and Mus of both sexes. Retinal cell types were detected by immunohistochemistry with cell type specific antibodies; sections were imaged by fluorescence and confocal microscopy. Gene and protein expression levels were analyzed by qRT-PCR, sc-RNA Seq, and western blot.
Results :
In response to acute retinal damage, two waves of cell proliferation were detected in Acomys: the first wave (24-96hpi) consisted exclusively of proliferating microglia, whereas the second wave (6-14dpi), included microglia and Müller glia. Reactive gliosis was significantly reduced in Acomys compared to Mus, with no induction of GFAP expression after injury. In Acomys retinas, proliferating microglia of various activation states were observed weeks after injury, whereas in Mus, the microglia returned to their resting ramified state by 10dpi. Additionally, by 14dpi, an increase of Brn3a+ ganglion cells was detected in Acomys, a subset of which were also positive for EdU.
Conclusions :
Our results show that Acomys mount a pro-regenerative response to inner retinal damage featuring an initial burst of microglial proliferation, followed by Müller glial proliferation. Importantly, reactive gliosis is not induced after retinal injury in Acomys. By 14dpi in Acomys there are signs of neurogenesis and recovery of retinal ganglion cells. To our knowledge, these data represent the first description of a mammal with the potential for retinal regeneration.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.