Purpose:
The role of microglia in age-related macular degeneration (AMD) remains undefined. We evaluate the distribution of activated microglia in AMD tissue in several retinal locations. We hypothesize that microglia are quiescent in areas where the retina is normal, but are active in areas undergoing degenerative changes.
Methods:
Donor eyes with AMD were obtained through the donor eye program of the Foundation Fighting Blindness. Eyes were fixed in 4% paraformaldehyde and 0.5% glutaraldehyde in phosphate buffer. Eyes were classified as early, intermediate, and end-stage AMD. End-stage AMD eyes were further divided into geographic atrophy (GA), choroidal neovascularization (CNV), or mixed. Normal donor eyes were purchased from Cleveland Eye Bank for age matched controls and fixed in the same buffer. Macrophotography, scanning laser ophthalmoscopy, and optical coherence tomography were used to better characterize regions of degenerate retina and the transition zones to normal retina. Cryosections of the macula, periphery, and transition zones were evaluated by indirect immunofluorescence, using monoclonal antibodies to activated microglia (mAB IBA-1) and a retinal cell marker. The distribution of IBA-1+ microglia in AMD donor eyes was compared to age matched normal eyes.
Results:
Preliminary results include two early stage eyes, one GA eye, and two control eyes. Early stage AMD eyes had abundant IBA-1+ microglia both in the inner retina and immediately below the retinal pigment epithelium (RPE). There were more IBA-1+ microglia on the optic nerve head and immediately surrounding it than in other areas of the inner retina. Otherwise, IBA-1+ microglia were distributed fairly evenly throughout the optic nerve and macula. The GA eye had a fair amount of IBA-1+ microglia both in the inner retina and below the RPE. Their distribution decreased in the periphery. IBA-1+ microglia were present to a lesser degree in control eyes. More microglia were associated with the optic nerve head than in other areas of the inner retina. Otherwise, IBA-1+ microglia were distributed fairly evenly from the optic nerve to the periphery. IBA-1+ microglia were present both in the inner retina and below the RPE.
Conclusions:
Preliminary data from AMD eyes showed a variable amount and distribution of IBA-1+ microglia in the macula, periphery, and transition zones in between. IBA-1+ microglia were abundant in the choroid and in areas showing no AMD pathology.
Keywords: age-related macular degeneration • microglia • pathology: human