High-throughput ultrastructural analysis of macular telangiectasia type 2

Introduction Macular Telangiectasia type 2 (MacTel), is an uncommon form of late-onset, slowly-progressive macular degeneration. Associated with regional M & uuml;ller glial cell loss in the retina and the amino acid serine synthesized by M & uuml;ller cells, the disease is functionally confined to a central retinal region - the MacTel zone.Methods We have used high-throughput multi-resolution electron microscopy techniques, optimized for disease analysis, to study the retinas from two women, mother and daughter, aged 79 and 48 years respectively, suffering from MacTel.Results In both eyes, the principal observations made were changes specific to mitochondrial structure both outside and within the MacTel zone in all retinal cell types, with the exception of those in the retinal pigment epithelium (RPE). The lesion areas, which are a hallmark of MacTel, extend from Bruch's membrane and the choriocapillaris, through all depths of the retina, and include cells from the RPE, retinal vascular elements, and extensive hypertrophic basement membrane material. Where the M & uuml;ller glial cells are lost, we have identified a significant population of microglial cells, exclusively within the Henle fiber layer, which appear to ensheathe the Henle fibers, similar to that seen normally by M & uuml;ller cells.Discussion Since M & uuml;ller cells synthesize retinal serine, whereas retinal neurons do not, we propose that serine deficiency, required for normal mitochondrial function, may relate to mitochondrial changes that underlie the development of MacTel. With mitochondrial changes occurring retina-wide, the question remains as to why the M & uuml;ller cells are uniquely susceptible within the MacTel zone.