Abstract
Purpose :
Adult zebrafish are capable of functional retinal regeneration following damage, and a current goal of vision science is to stimulate or permit a similar process in mammals as a means to treat retinal disease and trauma. Ideally such a process would reconstitute the stereotyped, two-dimensional topographic patterns of specific retinal cell types, which are functionally important for appropriate visual representation of the corresponding region of the visual field. An excellent example in humans is the cone-rich fovea, essential for high-acuity color vision. Stereotyped, global topographic patterns of specific retinal cell types are also found in the zebrafish, particularly for the cone types expressing tandemly-replicated opsin genes. For example, lws1 (long wavelength sensitive 1) is expressed predominantly in ventral and nasal retina, while lws2 is expressed in central and dorsal retina. Here we examined whether topographic patterns of retinal neurons are restored following retinal regeneration in zebrafish.
Methods :
Adult zebrafish carrying transgenic reporters for specific cell types were subjected to a retinal lesion that destroys all neurons but spares glia, via intraocular injection of the neurotoxin ouabain. Retinas were harvested at selected timepoints following the injection, mounted whole or sectioned, and imaged by confocal microscopy. One transgenic line used, lws:PAC(H), reports lws1 (GFP) and lws2 (RFP). Topographic pattern analysis was performed by measuring the retinal area occupied by specific neuronal types as a proportion of total retinal area in control vs regenerated retinas.
Results :
The proportion of retina occupied by LWS1 cones, LWS2 cones, or both cone types was similar in regenerated vs. control retinas (p > 0.2 for all; n=3). However, regenerated retinas contained lws1 and lws2 co-expressing cones, which were not found in undamaged adult retinas. Additionally, centrally-located LWS1 cones were observed in regenerated but not control retinas.
Conclusions :
Regenerated retinas displayed some topographic features (proportions occupied by specific cone types) that matched those of controls, as well as some features (co-expression of lws1 and lws2, and LWS1 cones present in central retina) that did not. This suggests that patterning mechanisms may be somewhat distinct from those operating during development and growth.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.