Evaluation of proliferating cell abundance and phenotypes in proliferative diabetic retinopathy

• Published in: Graefe's archive for clinical and experimental ophthalmology 2015-02, Vol.253 (2), p.229-236
• Main Authors: Feist, Richard M., King, Jeffery L., Mason, John O., Morris, Robert E., Guidry, Clyde
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Basic Science; Biomarkers - metabolism; Cell Count; Cell Proliferation; Diabetic retinopathy; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; Epiretinal Membrane - metabolism; Epiretinal Membrane - pathology; Female; Fluorescent Antibody Technique, Indirect; Glial Fibrillary Acidic Protein - metabolism; Glutamate-Ammonia Ligase - metabolism; Humans; Ki-67 Antigen - metabolism; Male; Medicine; Medicine & Public Health; Middle Aged; Ophthalmology; Phenotype
• ISSN: 0721-832X; 1435-702X
• DOI: 10.1007/s00417-014-2787-z

Background The aim of this work is to evaluate the abundance, origins, and phenotypes of actively proliferating cells in proliferative diabetic retinopathy (PDR). Methods Eleven epiretinal membranes from patients undergoing surgery for PDR were evaluated by indirect immunofluorescence for evidence of cell proliferation using the nuclear cell proliferation marker Ki67 and for cell identities using glial fibrillary acidic protein (GFAP), glutamine synthetase, and α-smooth muscle actin (αSMA). Results Ki67 positivity was consistently rare in PDR epiretinal membranes at 3.02 ± 1.42 % of the total cell population. The majority of the Ki67-positive cells were also positive for GFAP (74.0 %) with lower proportions positive for αSMA (30.7 %) and glutamine synthetase (1.5 %). Co-localization studies using glial and myoid markers revealed that virtually all (92 %) of the αSMA-positive cells are also GFAP positive and thus derive from glia. Conclusions Entry into cell cycle and thus cell proliferation appears to be a rare phenomenon in PDR involving only a small percentage of the total cell population. Glia and/or glial-derived myofibroblasts appear to be the predominate cell types in epiretinal scar tissues and also account for the majority of the actively proliferating cells.