Abstract
Purpose: :
To test whether regeneration of retinal pigment epithelium (RPE) after sodium iodate damage is enhanced in MRL/MpJ "healer" mice.
Methods: :
The RPE of MRL/MpJ and control AKR/J mice was damaged by retro-orbital sodium iodate injection. Visual function was assessed by electroretinography. RPE structural integrity was evaluated by anti-RPE65 immunohistochemistry and phalloidin staining in cryosections and posterior eye whole mounts, respectively.
Results: :
At five days following sodium iodate injection, MRL/MpJ and AKR/J mice visual responses decreased to 15-35% of the corresponding untreated baseline responses. This functional decline was accompanied by a loss of RPE65 staining in the central eyecup of both strains, indicating damage or loss of RPE cells in this region. Visual responses in MRL/MpJ mice increased to 65-75% and 125-130% of baseline at one and two months post-injection, respectively. RPE65 staining was restored at one month post-injection. By contrast, little functional or structural recovery was observed in AKR/J mice. Phalloidin staining at two days post-injection confirmed the loss of central and preservation of peripheral RPE in both strains, and revealed a transitional region characterized by shedding and restructuring of RPE cells, suggesting a similar initial response to damage. At one month post-injection, phalloidin staining showed substantial recovery of the central RPE in MRL/MpJ but not AKR/J mice.
Conclusions: :
RPE regeneration after sodium iodate damage is enhanced in MRL/MpJ mice compared to AKR/J mice. Further study of MRL/MpJ mice may identify factors that promote RPE regeneration and yield treatments for RPE loss in age-related macular degeneration and related diseases.
Keywords: retinal pigment epithelium • wound healing • regeneration