The Role of TRiC-enhanced Actin Folding in Leber Congenital Amaurosis.

Purpose: Mutations in TCP-1 ring complex (TRiC) have been associated with Leber Congenital Amaurosis (LCA). TRiC is involved in protein folding and has 8 essential subunits including CCT5. Herein, we studied the retina of TRiC mutant zebrafish to evaluate the possible role of impaired actin and tubulin folding in LCA.

Methods: The cct5 ${}^{tf212b}$ retina was histologically studied using Toluidine Blue staining as well as TUNEL, BrdU-labeling, and Phalloidin assays. Retinal organisation was assessed by quantification of the cellularity utilising DAPI.

Results: Laminar organization of cct5 ${}^{tf212b}$ retinas was intact. Enhanced apoptosis throughout the cct5 ${}^{tf212b}$ retina was not compensated by higher proliferation rates, leaving the cct5 ${}^{tf212b}$ retina smaller in size. Quantification of retinal layer cellularity demonstrated that specifically the numbers of the amacrine and the retinal ganglion cells were depleted, suggesting that the cct5 ${}^{tf212b}$ retina was not uniformly affected by the reduced actin folding.

Conclusion: Whereas the current literature suggests that LCA is predominantly affecting retinal photoreceptor cells and the retinal pigment epithelium, cct5 ${}^{tf212b}$ analyses demonstrated the important role of folding of actin by TRiC, suggesting that cct5 ${}^{tf212b}$ is a useful tool to specifically analyze the role of F-actin filaments in the context of LCA.