Abstract
Purpose :
In humans, glaucoma, piqued by sensitivity to intraocular pressure (IOP), ultimately leads to sectorial degeneration of retinal ganglion cells (RGCs). However, sectorial loss of RGCs is not always observed in animal models of glaucoma. The reason for this discrepancy is unclear. Here, we describe the spatial distribution of RGC subtypes and the relationship of morphological and physiological features to their position in the retina. Furthermore, we determine the influence of elevated IOP on RGC subtypes within each retinal quadrant.
Methods :
IOP was unilaterally elevated by 30% for 2 weeks by microbead occlusion of aqueous outflow, and the fellow eye was injected with an equal volume of saline. We previously detected dendritic pruning and physiological changes at 2 weeks of IOP elevation. Whole retinas were dissected out and prepared for electrophysiology. RGCs with large somas were targeted for intracellular recording and passively filled with ALEXA555. RGCs were typified based on light response and morphological characteristics. Whole retinas were imaged and stitched using a STORM Ti2-E microscope and Nikon Elements software. Dendritic arbors of filled cells were traced in ImageJ, and we assessed dendritic area and branch points. Retinas were reconstructed in 3D and oriented using the gradient of s-opsin staining for spatial analysis.
Results :
αON-S, αOFF-S, and αOFF-T RGCs are randomly distributed along the dorsal/ventral (p = 0.45) and nasal/temporal (p = 0.35) retina. Spatial distribution of these RGC subtypes did not differ between IOP-elevated and naïve eyes of WT mice. Spatial location was also independent of morphological and physiological characteristics, including the number of branch points, dendritic area, and light-evoked spike rate. Branch points for any RGC subtype was not predicted by the location of RGCs (dorsal/ventral p = 0.24; nasal/temporal p = 0.95). Likewise, dendritic area was found to be independent of location (dorsal/ventral p = 0.33; nasal/temporal p = 0.79). Similarly, spike rate is independent of the location of the RGC (dorsal/ventral p = 0.60; nasal/temporal p = 0.11).
Conclusions :
These results show that αON-S, αOFF-S, and αOFF-T RGCs are randomly distributed across the retina. Furthermore, this distribution is not affected by 2 weeks of elevated IOP. Finally, morphological and physiological characteristics of the RGCs are independent of location.
This is a 2020 ARVO Annual Meeting abstract.