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2017 ; 58
(3
): 1352-1367
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Subretinal Glial Membranes in Eyes With Geographic Atrophy
#MMPMID28249091
Edwards MM
; McLeod DS
; Bhutto IA
; Grebe R
; Duffy M
; Lutty GA
Invest Ophthalmol Vis Sci
2017[Mar]; 58
(3
): 1352-1367
PMID28249091
show ga
PURPOSE: Müller cells create the external limiting membrane (ELM) by forming
junctions with photoreceptor cells. This study evaluated the relationship between
focal photoreceptors and RPE loss in geographic atrophy (GA) and Müller cell
extension into the subretinal space. METHODS: Human donor eyes with no retinal
disease or geographic atrophy (GA) were fixed and the eye cups imaged. The
retinal posterior pole was stained for glial fibrillary acidic protein (GFAP;
astrocytes and activated Müller cells) and vimentin (Müller cells) while the
submacular choroids were labeled with Ulex Europaeus Agglutinin lectin (blood
vessels). Choroids and retinas were imaged using a Zeiss 710 confocal microscope.
Additional eyes were cryopreserved or processed for transmission electron
microscopy (TEM) to better visualize the Müller cells. RESULTS: Vimentin staining
of aged control retinas (n = 4) revealed a panretinal cobblestone-like ELM. While
this pattern was also observed in the GA retinas (n = 7), each also had a
distinct area in which vimentin+ and vimentin+/GFAP+ processes created a
subretinal membrane. Subretinal glial membranes closely matched areas of RPE
atrophy in the gross photos. Choroidal vascular loss was also evident in these
atrophic areas. Smaller glial projections were noted, which correlated with
drusen in gross photos. The presence of glia in the subretinal space was
confirmed by TEM and cross cross-section immunohistochemistry. CONCLUSIONS: In
eyes with GA, subretinal Müller cell membranes present in areas of RPE atrophy
may be a Müller cell attempt to replace the ELM. These membranes could interfere
with treatments such as stem cell therapy.