Abstract
Purpose :
Investigating RPE regeneration holds promise for advancing regenerative approaches to address disorders and injuries involving RPE dysfunction. Our purpose is to unveil retinal structural and functional disparities between spiny mice (Acomys) and house mice (Mus). Acomys stands out for its remarkable capacity to completely regenerate various tissues. Through laser-induced injury, we aim to assess the comparative impact of such injuries on the retinas of African spiny mice and C57BL/6 mice.
Methods :
Retinal structure and function in Mus and Acomys were compared by spectral-domain optical coherence tomography (SD-OCT) and electroretinogram (ERG) analyses. We used an OCT-guided laser module (Micron-4; Phoenix Technology Group) to apply focal laser burns in both Acomys and C57BL/6 mice, disrupting the RPE and Bruch’s membrane located two- or three-disc diameters from the optic nerve. The injury site was monitored for periods of 7- and 14-days post-laser injury. To visualize choroidal neovascularization (CNV) related fluorescence leakage resulting from laser burns, we implemented Fundus Fluorescein Angiography (FFA). Concurrently, RPE/Choroid flat mounts underwent immunostaining with the proliferative marker Ki67.
Results :
Our findings reveal striking similarities in the retinal structure between spiny mice and the conventional laboratory mouse (Mus), supported by electroretinograms indicating normal retinal function in spiny mice. Notably, 14 days post laser-induced injury to the retinal pigment epithelium (RPE) and choroid, comprehensive imaging via fundus and spectral-domain optical coherence tomography (SD-OCT) demonstrated a remarkably accelerated healing response in Acomys compared to Mus. Fundus Fluorescein Angiography (FFA) underscored this divergence, illustrating vascular leakage in Mus but not in Acomys. Additionally, our immunoassay conducted 48 hours post-injury at the lesion site unveiled heightened expression of the Ki67 protein, indicative of increased cellular proliferation in Acomys compared to Mus.
Conclusions :
These observations collectively highlight the superior regenerative potential and distinctive healing mechanisms exhibited by the African spiny mouse in response to retinal injury, offering valuable insights for future regenerative studies and therapeutic applications.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.