Glial cells and collagens in epiretinal membranes associated with idiopathic macular holes.
OBJECTIVE
To investigate the identity of collagens and cellular components in the epiretinal membrane (ERM) associated with full-thickness idiopathic macular hole and their clinical relevance.


METHODS
Pars plana vitrectomy with the peeling of internal limiting membrane and ERM was performed by 2 surgeons in 40 eyes with idiopathic macular holes. The clinical data were reviewed and the surgical specimens were processed for flat-mount and immunohistochemical analysis.


RESULTS
Epiretinal membrane is a GFAP-positive gliotic and fibrotic scar which contains newly formed Type I, III, and V collagens. Type VI collagen was not observed. Colocalization studies found cells coexpressing GFAP/CRALBP, GFAP/α-SMA, and α-SMA/CRALBP, which are consistent with transdifferentiation of Müller cells into fibroblasts and myofibroblasts. The clinically significant ERMs can be divided into two groups according to the amount of cells in ERM: sparse cellular proliferation and dense cellular proliferation. The latter group is associated with a higher chance of surgical difficulty during internal limiting membrane peeling (P = 0.006). Preoperative and postoperative visual function were not affected by the density of the cellular proliferation.


CONCLUSIONS
Retinal glial cells, probably transdifferentiated Müller cells, are involved in the formation of full-thickness macular hole-associated ERMs by a gliotic and fibrotic process. Such ERMs contain newly formed Type I, III, and V collagen depositions. The cell density of ERM affects its biomechanical properties and determines the difficulty of ERM peeling.
*Department of Ophthalmology, University Medical Center Groningen, Groningen, the Netherlands; †W. J. Kolff Institute, Graduate School of Medical Sciences, University of Groningen, Groningen, the Netherlands; ‡Tianjin Medical University Eye Hospital, Tianjin, China; and §Department of Biomedical Engineering, University of Groningen, Groningen, the Netherlands.
Shao-Chong
SC
Bu
Roel
R
Kuijer
Roelofje J
RJ
van der Worp
Eveline A
EA
Huiskamp
Victor W
VW
Renardel de Lavalette
Xiao-Rong
XR
Li
Johanna M M
JM
Hooymans
Leonoor I
LI
Los
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002352:Carrier Proteins / Q000378:metabolism; D058450:Endotamponade; D019773:Epiretinal Membrane / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D005260:Female; D024022:Fibrillar Collagens / Q000378:metabolism*; D005355:Fibrosis; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D012167:Retinal Perforations / Q000150:complications* / Q000175:diagnosis / Q000601:surgery; D013459:Sulfur Hexafluoride / Q000008:administration & dosage; D014019:Tissue Donors; D041623:Tomography, Optical Coherence; D014821:Vitrectomy
C020932:11-cis-retinal-binding protein; C541116:ACTA2 protein, human; D000199:Actins; D002352:Carrier Proteins; D024022:Fibrillar Collagens; D005904:Glial Fibrillary Acidic Protein; D013459:Sulfur Hexafluoride