Differential expression of GFAP in early v late AMD: a quantitative analysis

Glial fibrillary acidic protein (GFAP) is an established indicator of retinal stress; its expression in retinal astrocytes and Müller cells has been demonstrated to be modulated by cytokines and retinal pathology, including age related macular degeneration (AMD). This study aims to quantify the modulation of GFAP expression in retinas with drusen and atrophic AMD versus normal age matched controls.

Following a histopathological survey, 17 donor retinas were classified into four groups: drusen (n=5), geographic atrophy (GA) (n=6), aged normal (n=3), and young normal (n=3). Paramacular cryosections were immunolabelled with GFAP antibody, examined by confocal microscopy, and quantified by NIH digital image analysis. Groups were matched for potential confounding factors including age, sex, and postmortem delay.

A significant increase in GFAP immunolabelling of macroglia was noted in aged normal compared with young normal retinas (p<0.04). Upregulation of GFAP immunoreactivity involving astrocytes was observed in drusen retinas compared with control retinas (p<0.03). GFAP was also upregulated in retinas with GA compared with controls (p<0.05) and in retinas with GA compared with drusen (p<0.04), both involving Müller cells. Discrete regions of GFAP upregulation in Müller cells were associated with drusen formation. In GA specimens atrophied retinal pigment epithelium (RPE) was substituted by GFAP immunoreactive Müller cell processes (gliosis).

This study provides a quantitative assessment of GFAP modulation in ageing and AMD affected retinas. Morphological observations were consistent with quantitative analyses indicating differential modulation of GFAP immunoreactivity in inner and outer retina. Upmodulation of GFAP in inner retina and astroglial processes was predominantly associated with drusen, while in outer retina Müller glia upmodulation of GFAP was associated with disruption of the RPE and blood-retinal barrier.