Retinal cell mapping could promote accurate therapies for blindness: Scientists

Researchers discovered distinct variances between the cells that make up retinal tissue, which might aid in the development of tailored medicines to treat a variety of disorders affecting the retina.

A team of researchers from the National Eye Institute published their findings in the journal ‘Proceedings of the National Academy of Sciences.’ National Eye Institute (NEI) researchers revealed five subpopulations of retinal pigment epithelium (RPE), a layer of tissue that nourishes and maintains the retina’s light-sensing photoreceptors.

The researchers used artificial intelligence to evaluate photos of RPE at single-cell resolution to produce a reference map that locates each subpopulation within the eye. The findings of the study were reported in the Proceedings of the National Academy of Sciences.

“These results provide a first-of-its-kind framework for understanding different RPE cell subpopulations and their vulnerability to retinal diseases, and for developing targeted therapies to treat them,” said Michael F. Chiang, M.D., director of the NEI, part of the National Institutes of Health.

The findings “will help us develop more precise cell and gene therapies for specific degenerative eye diseases,” said the study’s lead investigator, Kapil Bharti, PhD, who directs the NEI Ocular and Stem Cell Translational Research Section.

When light strikes the rod and cone photoreceptors that line the retina at the rear of the eye, vision starts. Once triggered, photoreceptors convey messages to multiple brain areas via a complicated network of other retinal neurons that converge at the optic nerve. The RPE forms a monolayer underneath the photoreceptors, one cell deep.

In RPE cells, age and illness can produce metabolic alterations that contribute to photoreceptor degradation. The impact of these RPE modifications on vision varies greatly depending on the severity and location of the RPE cells inside the retina.

For example, late-onset retinal degeneration (L-ORD), for example, mostly affects the peripheral retina and, as a result, peripheral vision.

Each RPE cell’s morphometry characteristics were determined, which amounted to approximately 2.8 million cells per donor on average; 47.6 million cells were studied in total.The programme calculated the area, aspect ratio (width to height), hexagonality, and number of neighbours for each cell.

Previous research has linked RPE function to the tightness of cellular junctions; the more packed the connections, the better for signalling cellular health.

They discovered five unique RPE cell subpopulations, known as P1-P5, based on morphometry, and grouped them in concentric circles around the fovea, which is the centre of the macula and the most light-sensitive part of the retina.

When compared to RPE in the periphery, foveal RPE is precisely hexagonal and more densely packed, with a greater number of neighbouring cells.

Surprisingly, they detected a ring of RPE cells (P4) in the peripheral retina, with a cell area remarkably comparable to that of the RPE in and around the macula.

The presence of the P4 subpopulation highlights the diversity within the retinal periphery, suggesting that there may be functional differences among RPE that we are currently unaware of,” said the study’s first author, Davide Ortolan, PhD, a NEI Ocular and Stem Cell Translational Research Section research fellow. “Future research is needed to better understand the role of this subgroup.”

They then examined RPE from cadavers with AMD. Due to disease damage, foveal (P1) RPE was often missing, and differences between cells in the P2-P5 subpopulations were not statistically significant.

Overall, AMD RPE subpopulations were longer than RPE cells that were not impacted by AMD.

They studied ultrawide-field fundus autofluorescence pictures from individuals with choroideremia, L-ORD, or a retinal degeneration with no known molecular origin to further investigate the concept that distinct retinal degenerations impact particular RPE subpopulations.

Despite the fact that these experiments were done at a particular moment in time, they showed that various RPE subpopulations are susceptible to different forms of retinal degenerative disorders.