Researchers have identified distinct differences among the cells
comprising a tissue in the retina, findings that could help develop precise
therapies for retinal diseases.
In a new study, researchers form the US National Eye Institute (NEI)
have identified distinct differences among the cells comprising a tissue in the
retina that is vital to human visual perception. The scientists discovered five
subpopulations of retinal pigment epithelium (RPE), a layer of tissue that
nourishes and supports the retina’s light-sensing photoreceptors. Using
artificial intelligence (AI), the researchers analysed images of RPE at
single-cell resolution to create a reference map that locates each
subpopulation within the eye. The ground-breaking research, which was recently
published in Proceedings of the National Academy of Science, could help find
more precise cell and gene therapies for retinal diseases.
Age and disease can cause metabolic changes in RPE cells that can lead
to photoreceptor degeneration. The impact on vision from these RPE changes
varies dramatically by severity and where the RPE cells reside within the
retina. For example, late-onset retinal degeneration (L-ORD) affects mostly
peripheral retina and, therefore, peripheral vision. Age-related macular degeneration
(AMD), a leading cause of vision loss, primarily affects RPE cells in the
macula, which is crucial for central vision.
The researchers aimed to determine if there are different RPE
subpopulations that might explain the wide spectrum of retinal disease
phenotypes. They used AI to analyse RPE cell morphometry, the external shape
and dimensions of each cell. They trained a computer using fluorescently
labelled images of RPE to analyse the entire human RPE monolayer from nine
cadaver donors with no history of significant eye disease.
Morphometry features were calculated for each RPE cell – on average,
about 2.8 million cells per donor; 47.6 million cells were analysed in total.
The algorithm assessed each cell’s area, aspect ratio (width to height),
hexagonality, and number of neighbours. Previous studies had suggested that RPE
function is tied to the tightness of cellular junctions; the more crowded, the
better for indicating cellular health.
Based on morphometry, they identified five distinct RPE cell
subpopulations, referred to as P1-P5, organised in concentric circles around
the fovea, which is the centre of the macula and the most light-sensitive
region of the retina. Compared to RPE in the periphery, foveal RPE tend to be
perfectly hexagonal and more compactly situated, with higher numbers of
neighbouring cells.
Next, they analysed RPE from cadavers with AMD. Foveal (P1) RPE tended
to be absent due to disease damage, and the differences among cells in the
P2-P5 subpopulations were not statistically significant. Overall, the AMD RPE
subpopulations tended to be elongated relative to RPE cells not affected by
AMD.
To further test the hypothesis that different retinal degenerations
affect specific RPE subpopulations, they analysed ultrawide-field fundus
autofluorescence images from patients affected by chloridaemia, L-ORD, or a
retinal degeneration with no identified molecular cauase. While these studies
were conducted at a single point in time, they still demonstrated that
different RPE subpopulations are vulnerable to different types of retinal
degenerative diseases.
Age-related morphometric changes also may appear in some RPE subpopulations
before they’re detectable in others. These finding could help inform future
studies using non-invasive imaging technologies, such as adaptive optics, which
resolve retinal cells in unprecedented detail and could potentially be used to
predict changes in RPE health in living patients.
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European Journal of Case Reports and Clinical Images is an international open-access journal publi
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