Abstract
Purpose :
The capacity for retinal regeneration varies widely across vertebrate species, however to date no mammal has been shown to have this ability. Identifying a mammal with a propensity for retinal regeneration could provide valuable mechanistic insights and inform therapeutic approaches to treat blinding retinal diseases. The common spiny mouse, Acomys cahirinus, has been shown to have remarkable regenerative ability in the skin, kidney, muscle, heart, and spinal cord. Here, we present an overview of Acomys retinal anatomy and an initial assessment of its response to acute retinal damage as compared to the non-regenerator Mus musculus.
Methods :
All procedures were performed in accordance with guidelines established by the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Retinal sections were prepared from dissected eyes of adult Acomys and Mus. Retinal cell types were detected by immunohistochemistry with cell type specific antibodies; sections were imaged by fluorescence and confocal microscopy and assessed for cell number and morphology. Acute damage of Acomys and Mus retinal ganglion and amacrine cells was induced via intravitreal injection of 100mM NMDA. Cell death was detected using the TUNEL assay. Cell proliferation was detected using immunolabeling for PCNA, MCM2, and EdU incorporation. Gene expression following acute damage as analyzed via qRT-PCR.
Results :
In general, retinal cell type abundance, morphology, and positioning were comparable between Acomys and Mus, however Acomys retinas displayed lower cone and horizontal cell density, as well as altered laminar location of some bipolar cell bodies. In response to acute damage, Acomys retinas contained more proliferating cells compared to Mus, a subset of which co-localized with markers of Müller glia. Additionally, Acomys (but not Mus) displayed increased expression of retinal regeneration genes in response to damage. At ten days post injury, recovery of Pax6+ ganglion and amacrine cells was evident in Acomys but not Mus retinas.
Conclusions :
Our results show that A. cahirinus mounts a pro-regenerative response to inner retinal damage that includes increased cellular proliferation, induction of regenerative gene expression, and recovery of Pax6+ neurons. To our knowledge, these data represent the first description of a mammal with the potential for retina regeneration.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.