Fig. 6.

Treatment with the ketogenic diet rescues photoreceptor cell survival in the arRP preclinical mouse. (a) Histological analysis of the retinas of Pde6ɑ^D670G mice on normal chow diet (gray) compared to Pde6ɑ^D670G mice provided the ketogenic diet (green) shows a significant increase in the thickness of the outer nuclear layer (ONL) by number of photoreceptor cell nuclei in mice treated with the ketogenic diet at one month of age, one-week post-dietary treatment. Results are displayed as a morphometric quantification (spider graph) of ONL layer thickness superior (left) and inferior (right) to the optic nerve head (ONH). Wild-type mice have an ONL thickness of approximately 10 nuclei. ***p < 0.001 [Student's t-test]. N = 8 eyes each group, with multiple ONL thickness counts per eye as described in Methods. Error bars = SEM. (b) Representative traces of the scotopic 0.1 (flash strength in cd·s·m⁻²) dim-light rod-specific electroretinography (ERG; left) shows no significant difference in the rod photoreceptor cell response in Pde6ɑ^D670G mice treated with the ketogenic diet (green) in comparison to untreated Pde6ɑ^D670G mice (gray) at one month of age. Representative traces of the scotopic 1.0 (flash strength in cd·s·m⁻²) global electroretinography (ERG; left) shows some rescue of the global visual response in Pde6ɑ^D670G mice treated with the ketogenic diet (green) in comparison to wild-type controls (black) and untreated Pde6ɑ^D670G mice (gray) at one month of age. Quantification of ERGs from a cohort of mice shows no significant visual rescue of (c) the rod photoreceptor cell response, (d) the maximum scotopic a-wave response, or (e) the maximum scotopic b-wave response in mice treated with the ketogenic diet (green) in comparison with wild-type controls (black) or untreated Pde6ɑ^D670G mice (gray) at one month of age, although there was a trend toward an increased a- and b-wave maximal response. N = 5 WT, 6 arRP, 6 arRP + ketogenic diet mice.