title: Müller cell changes in human diabetic retinopathy.
abstract: Vascular cells may not be the only cells affected by diabetes in the retina. In particular, abnormalities of the b-wave of the electroretinogram in diabetic patients with absent or minimal microangiopathy have pointed to possible dysfunction of Müller cells, the principal glia of the retina. In this study, we sought evidence for diabetes-induced Müller cell abnormalities by testing the expression of three proteins (Bcl-2, glutamine synthetase [GS], and glial fibrillar acidic protein [GFAP]) that are solely or predominantly expressed in Müller cells and show a reproducible pattern of changes in the context of retinal injuries or degenerations. Retinas obtained postmortem from a total of 14 donors aged 65 +/- 6 years with 10 +/- 4 years of diabetes and histological evidence of microangiopathy and 18 age-matched nondiabetic donors were examined by immunohistochemistry and immunoblotting. The typical Müller cell pattern of Bcl-2 and GS immunostaining was similar for both intensity and distribution in the nondiabetic and diabetic retinas, as were the levels of the two proteins. In contrast, GFAP staining, largely confined to the most proximal retina in the nondiabetic donors, was in most diabetic retinas present along the entire length of the Müller cell processes, throughout the outer retina. Accordingly, the level of GFAP was increased in the diabetic retinas (161 +/- 106 densitometric units/microg protein vs. 55 +/- 45 in the nondiabetic retinas, P = 0.03). These data provide evidence for selective biosynthetic changes of Müller glial cells in diabetes. Because Müller cells produce factors capable of modulating blood flow, vascular permeability, and cell survival, and their processes surround all blood vessels in the retina, a possible role of these cells in the pathogenesis of retinal microangiopathy deserves to be investigated.
authors.affiliation: Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mizutani
authors.forename: C
authors.initials: C
authors.lastname: Gerhardinger
authors.forename: M
authors.initials: M
authors.lastname: Lorenzi
mesh_terms: D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002417:Cattle; D002645:Chickens; D015331:Cohort Studies; D003930:Diabetic Retinopathy / Q000201:enzymology / Q000473:pathology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis*; D005974:Glutamate-Ammonia Ligase / Q000032:analysis*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D011817:Rabbits; D012160:Retina / Q000166:cytology / Q000473:pathology*; D014019:Tissue Donors; D051020:bcl-X Protein
chemical_list: D000911:Antibodies, Monoclonal; C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D007106:Immune Sera; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D005974:Glutamate-Ammonia Ligase