RPE transdifferentiation revealed in AMD

Jun 30 2015

By Lynda Williams, Senior medwireNews Reporter

Subducted and melanotic cells in the eyes of patients with advanced age-related macular degeneration (AMD) derive from two distinct retinal pigment epithelium (RPE) phenotypes, research shows.

Christine Curcio, from the University of Alabama in Birmingham, USA, and co-workers examined for transdifferentiation in donor eyes from AMD patients, of which 13 had geographical atrophy (GA) and 39 choroidal neovascularisation (CNV).

The team used the anatomical markers to characterise subducted and melanotic cells found outside the RPE layer and unattached to basal lamina or a basal laminar deposit.

Analysis showed that the subducted cells found in the space between the RPE and Bruch’s membrane had RPE melanosomes.

The researchers identified multiple “credible transitional forms” from RPE cells overlying the subducted cells. This included “atrophy with basal laminar deposit” cells in 32.2% of GA and 37.0% of CNV eyes, “dissociated” in 22.0% and 21.7%, “nonuniform” in 22.0% and 23.9%, and “sloughed” in 10.2% and 4.3%, respectively.

In addition, CNV scarring contained melanotic cells with spherical melanosomes placed near entombed RPE with spindle-shaped and spherical melanosomes.

Of the subretinal melanotic cells, 40.0% were associated with “atrophy with basal laminar deposit”, 36.8% with “atrophy without basal laminar deposit” and 20.6% with entombed RPE.

“’Dissociated’ RPE within atrophic areas may be the source of ‘Subducted’ cells”, while “‘[e]ntombed’ RPE within fibrovascular and fibrocellular scars may be the source of ‘Melanotic’ cells”, Curcio et al hypothesise in Investigative Ophthalmology & Visual Science.

The researchers conclude: “Our assessment demonstrates above all the amazing phenotypic diversity of RPE, a cell at the center of AMD.

“By highlighting transdifferentiation and its many implied molecular mechanisms, our data raise expectations for model systems used to test therapies for nonneovascular AMD, as these historically emphasize depigmentation and atrophy.”

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