Abstract
Purpose :
RPE basal infoldings are microvillous membrane specializations to optimize surface area for ion transport and exchange of metabolites with the choroidal circulation. The fovea is supplied by the choroid, while mixed rod-cone areas are supplied additionally by the retinal circulation. We hypothesize that the basal RPE will differ in areas with differing photoreceptor content. We investigated basal infoldings (BI) in foveal and parafoveal regions of human RPE.
Methods :
Rapidly preserved foveal (~160 µm eccentricity) and parafoveal (~850 µm eccentricity) tissue from 21-year-old and 53-year-old organ donors, respectively, were vertically sectioned using scanning block-face EM at 5 x 5 x 50 nm voxel resolution. BI were manually reconstructed in 7.5 x 7.5 µm sampling regions at the basolateral RPE using TrakEM2. Morphometric analysis of density (# per mm of basal lamina) and surface area (mm2 per sampling region) were performed using ImageJ and Dragonfly 2020.2 (Object Research Systems).
Results :
BI resemble elongated filopodia that appear to originate and extend from a consistent level of the cell body and extend towards the RPE basal lamina (Figure). Foveal BI had fine ridge-like profiles (A1). Parafoveal BI were elaborate (D1) with whorls that extended as far as the nuclear envelope (D2, E2), in contrast to straighter and non-convoluted infoldings under the nuclei of foveal RPE (A2, B2). The density of BI was higher in the fovea than parafovea (4624 ± 594 vs. 2784 ± 359 infoldings/ mm, P <0.001). The surface area was 39% higher in the fovea compared to parafovea (838.9 vs. 602.3 μm2). We also identified electron-dense punctate material that tend to localize at the basal RPE cell body, in a regularly-spaced pattern (B2). The internal structure of this material resembled disorganized cristae of mitochondria.
Conclusions :
Our initial findings suggest that the exchange capacity of foveal RPE may be significantly higher than parafoveal RPE. However, we cannot exclude that age difference in our samples could also be a factor in these morphological differences. To answer this question, ongoing studies will match regions and ages to the current samples (fovea of 21-year-old and parafovea of 53-year-old) and expand sample size with deep-learning assisted methods.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.