Hyperreflective Foci, Optical Coherence Tomography Progression Indicators in Age-Related Macular Degeneration,...

Area of Science:

• Ophthalmology
• Cell Biology
• Histopathology

Background:

• Hyperreflective foci (HRF) on optical coherence tomography (OCT) imaging are associated with disease progression in advanced age-related macular degeneration (AMD).
• These HRF are partly attributed to ectopic retinal pigment epithelium (RPE) cells located outside their normal layer.
• The molecular characteristics and migratory pathways of these ectopic RPE cells remain incompletely understood.

Purpose of the Study:

• To investigate if ectopic RPE cells contributing to HRF in AMD are molecularly distinct from healthy in-layer RPE cells.
• To determine if the migration of ectopic RPE cells follows the path of Müller glia within the retina.
• To explore the potential for RPE transdifferentiation in AMD pathogenesis.

Main Methods:

• Clinical OCT imaging of 61 eyes from 44 AMD patients over a 4.7-year follow-up.
• Ex vivo OCT and histological analysis of 20 donor eyes with varying stages of AMD.
• Immunohistochemical staining for retinoid (RPE65, CRALPB) and immune (CD68, CD163) markers in RPE cells.

Main Results:

• RPE plumes, a type of HRF, showed dynamic morphology with a 40% resolution rate.
• Ectopic RPE cells exhibited loss of retinoid marker immunoreactivity and gain of immune marker immunoreactivity.
• The trajectories of RPE plumes and cellular debris paralleled Müller glia, with plume cells contacting retinal capillaries.

Conclusions:

• HRF serve as indicators, not predictors, of AMD disease activity.
• Molecular changes in RPE cells, including loss and gain of function, initiate in individual cells and extend to abnormal phenotypes.
• Evidence suggests RPE transdifferentiation, potentially driven by ischemia, supporting an epithelial-mesenchyme transition process that may guide future AMD biomarkers and therapies.