Geckos as a new model system to understand fovea-genesis

Abstract

Purpose : The fovea is a specialized pit in the retina responsible for high acuity vision. Disorders leading to its degradation or those inhibiting its typical development cause irreversible, central vision loss and are difficult to study due to a lack of accessible foveated model systems. We are investigating the potential for small, easily maintained, diurnal lizards to be used as models since they possess a fovea similar to humans.

Methods : An embryo staging series for the foveated gecko, Phelsuma laticauda, was created using morphological criteria outlined by Sanger et al., 2008 and Griffing et al, 2019. Embryos (n=110) were collected at various timepoints between 0-46 days post oviposition. Eggs were maintained at 28C temperature with a humidity around 60%. Embryos were fixed, embedded in paraffin, and eyes sectioned to capture key stages of retina and fovea development. H&E staining was used to characterize morphological changes in the retina (layer thickness, fovea depth, photoreceptor packing) while immunohistochemistry was used to distinguish cell types.

Results : We developed an embryological series for P. laticauda geckos to capture elements of foveal development. Similar to humans and other foveated reptiles, Phelsuma geckos undergo asymmetric changes in ocular shape during embryonic development. The temporal region of the eye that will eventually give rise to the temporal fovea transiently becomes elongated and then retracts as pit formation occurs. We also show that the incipient fovea retinal region appears to be developing at a faster rate than the peripheral retinal regions early in development prior to the eyes elongating (i.e., a plexiform layer is detected in the temporal retina before nasal and central regions). The fovea develops in the latter 3^rd of embryonic development (between stages 16/17), which is consistent with other foveated lizards and humans. By the time of hatching, Phelsuma geckos are independent and capable hunters able to thrive on their own without parental care.

Conclusions : P. laticauda foveal development shares many morphological similarities with humans. It is possible that many of the molecular and disease pathways are conserved as well. Molecular characterization of the developing gecko retina may confirm this and open up the possibility of using gene-editing to generate mutant phenotypes that replicate known foveal conditions in humans.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.