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

Abstract

Background/aims: 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. Methods: 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. Results: 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). Conclusion: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.

Abnormal vascularization in mouse retina with dysregulated retinal cholesterol homeostasis

“…GS is expressed constitutively in Müller cells (43), whereas GFAP is an intermediate filament protein upregulated in Müller cells in response to hypoxia, injury, and photoreceptor degeneration (44). Staining for GFAP was also reported in the RPE cells of patients with AMD (45). Anti-GFAP immunoreactivity was very low in the WT retina ( Figure 4L), but was elevated in Cyp27a1 -/-animals in lesion areas ( Figure 4D) and elsewhere ( Figure 4G), indicating general activation of Müller cells throughout the Cyp27a1 -/-retina.…”

Therapeutic Effect of Melatonin in Experimental Uveitis

“…47 GFAP up-regulation is a hallmark of reactive astrocytes 48 and retinal pathology modulates its expression. 49,50 Mü ller cells that do not express GFAP under physiological conditions are known to express GFAP in pathological situations. 51,52 The present results indicate that the injection of LPS provoked a significant alteration in retinal Mü ller cells, as shown by an increase in GFAP immunoreactivity that was prevented by melatonin.…”

Differential cellular expression of organic anion transporting peptides OATP1A2 and OATP2B1 in the human retina and brain: implications for carrier-mediated transport of neuropeptides and neurosteriods in the CNS

“…5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 14 In addition, to clarify whether the abundant OATP immunoreactivity in the GCL (Fig. 1A) is also present in retinal macroglial cells (astrocytes and Müller cells) localized in this layer [58], double staining experiments were performed in which the anti-OATP1A2 antibody was coincubated with an anti-glial fibrillary acidic protein, a glial marker. No colocalization of the OATP1A2-IR with the glia cell marker was found in these experiments (not shown).…”