Abstract
Purpose :
In this work, we assess in depth retinal features of the day-active Mongolian gerbil (Meriones unguiculatus) (MG), in particular with regard to the cone system. We found that the MG is a valuable alternative model to study retinal cone system physiology and pathophysiology, as the demands on human vision due to the diurnal lifestyle are very different from those on vision in nocturnal animals like mice, leading to several differences in retinal organization and function that are better mirrored in the MG.
Methods :
Retinal function and morphology in young adult MGs (2-3 postnatal months (PM)) (n=9) were compared with previously recorded data from young adult wild-type (wt) C57BL/6 mice (1-2 PM). Function was assessed via dark- and light-adapted single flash and flicker full-field electroretinography (ERG). Morphological data were obtained in vivo via angiography and optical coherence tomography (OCT) imaging, as well as ex vivo per immunohistochemistry on dorsal-ventral retinal cross-sections to label peanut agglutinin (PNA), rhodopsin, S-/M-opsins and MERTK. One-tailed paired student’s t-tests were used in statistical analyses.
Results :
While rod system responses were comparable between MGs and wts, cone system responses in the MGs were larger, more sensitive, presented higher flicker fusion frequencies (FFF), and showed substantial ON and OFF components. Morphologically, we found a uniform distribution of cone photoreceptor opsins throughout the retina of the MG, which were also individually expressed. Conversely, mice show a dorsoventral gradient of co-expressed M- and S-opsins. Moreover, the dorsally located visual streak (VS) region of the MG presented macula-like characteristics, such as an increased thickness of the inner (44%, p<0.01) and outer (10%, p<0.001) retinal layers in comparison to peripheral regions, and a higher density of cones (27%, p<0.05). In the outer retina, the outer nuclear layer was not substantially increased, while the outer segments of both rods and cones were significantly elongated (34%, p<0.05 and 56%, p<0,001, respectively). This was paralleled by an increased accumulation of MERTK-labelled phagosomes in the RPE (74%, p<0.01).
Conclusions :
The MG, due to its highly developed cone system and the formation of a VS, may thus be a superior model to investigate the physiology and pathophysiology of related human disorders and to validate potential therapeutic strategies in that context.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.