Department of Biology

University of Kentucky

Lexington, Kentucky

BASIC RESEARCH PROJECT

Retinal damage and regeneration in the African spiny mouse ( Acomys cahirinus ): a novel mammalian model for translational research

Research Interests

It is commonly believed that the ability to regenerate neurons in vertebrates is an exclusive property of non-mammalian species such as fish and amphibians. However, in recent years, spiny mice (Acomys) have become the focus of intense research for their enhanced wound repair and regenerative ability in many tissues. This raises the question of whether these mammals might regenerate retinal neurons in response to damage. We have obtained preliminary data that this may indeed be the case. The purpose of this project is to test the hypothesis that the spiny mouse possesses the capacity to regenerate retinal neurons in response to damage, and to take the first steps in determining the underlying biological mechanism. This study may identify promising avenues for promoting regeneration in human patients with retinal degenerative diseases.

Plans for 2023:

In the next funding period, our goal is to determine how the immune system shapes the regenerative response to retinal damage in Acomys. We will focus on two critical features of immune system responses that have been documented for fully regenerating species – inflammation and the activation of retinal microglia.

Specific Aims: In Specific Aim 1, we will characterize and compare the scale and timing of inflammatory signaling in Acomys and Mus in response to acute retinal damage. In Specific Aim 2, we will determine the role of microglia in the Acomys retinal regenerative response.

Progress in 2022:

Using several complementary methods to detect cell proliferation, we confirmed that NMDA damage to the inner retina elicits a significantly stronger proliferative response in Acomys compared to Mus, and this response persists through 48 hours post injury (hpi). Moreover, we found that some of the cell proliferation in Acomys is coming from the Müller glia, indicating that Acomys might use a similar mechanism to regenerate retinal cells as is observed in fully regenerating species such as zebrafish. Excitingly, we observed a large increase in expression of the critical regeneration factor Ascl1 in the injured Acomys (but not Mus) retina, demonstrating that Acomys does mount a pro-regenerative response to inner retinal damage.