RPE Cell and Sheet Properties in Normal and Diseased Eyes

Abstract

Purpose Previous studies of human retinal pigment epithelium (RPE) morphology found spatial differences in density: a high density of cells in the macula, decreasing peripherally. Because the RPE sheet is not perfectly regular, we anticipate that there will be differences between conditions and when and where damage is most likely to begin. The purpose of this study is to establish relationships among RPE morphometrics in age, cell location, and disease of normal human and AMD eyes that highlight irregularities reflecting damage. Methods Cadaveric eyes from 11 normal and 3 age-related macular degeneration (AMD) human donors ranging from 29 to 82 years of age were used. Borders of RPE cells were identified with phalloidin. RPE segmentation and analysis were conducted with CellProfiler. Exploration of spatial point patterns was conducted using the “spatstat” package of R. Results In the normal human eye, with increasing age, cell size increased, and cells lost their regular hexagonal shape. Cell density was higher in the macula versus periphery. AMD resulted in greater variability in size and shape of the RPE cell. Spatial point analysis revealed an ordered distribution of cells in normal and high spatial disorder in AMD eyes. Conclusions Morphometrics of the RPE cell readily discriminate among young vs. old and normal vs. diseased in the human eye. The normal RPE sheet is organized in a regular array of cells, but AMD exhibited strong spatial irregularity. These findings reflect on the robust recovery of the RPE sheet after wounding and the circumstances under which it cannot recover.

p62 /SQSTM1 coding plasmid prevents age related macular degeneration in a rat model

“…Our prior data indicate that AMD-like pathology in OXYS rats is strongly associated with age-related alterations of the RPE and glia, and may derive from an imbalance of immune processes, including chronic inflammation [ 10 , 11 ]. Normal RPE sheet is organized as a regular array of cells while upon AMD it exhibits strong spatial irregularity [ 20 ]. Other RPE changes typical for AMD include hypertrophy, multinucleation, and disruption of the hexagonal structure.…”

Acute Central Serous Chorioretinopathy

“…In aged human maculae, RPE cells increase in size and lose their regular hexagonal shape. 43 Studies of aging primate eyes have shown that mitochondrial elongation is observed within RPE cells located of the macular area, an indicator of increased metabolic stress. 44 In aged mouse eyes, RPE cells undergo multinucleation because of aborted mitosis, one of the mechanisms of cell death, and the contact with photoreceptor outer segments inhibits RPE cell proliferation.…”

Deep learning predicts function of live retinal pigment epithelium from quantitative microscopy

“…The RPE is a cellular monolayer, and RPE are of clinical interest, as shown by the fact that at least 11 investigational new drug-enabling (IND-enabling) or phase I clinical trial stage studies are using RPE to treat AMD (4). Additionally, the appearance of RPE cells within the monolayer is known to be critical to RPE function (5)(6)(7) and recently a phase I clinical trial used visual inspection of RPE by an expert technician as a biomanufacturing release criterion for implantation (8). RPE cell appearance is largely dictated by the maturity of junctional complexes between neighboring RPE cells and the characteristic pigmented appearance from melanin production (9).…”