Purpose: 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.
Conclusion: 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.
An epiretinal membrane associated with an idiopathic macular hole is a gliotic tissue containing newly formed Type I, III, and V collagens. Dense cellular proliferation in epiretinal membrane is associated with a higher chance of difficult internal limiting membrane peeling. Epiretinal membrane formation is a dynamic process in which glial cell activation and transdifferentiation are important.
*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.
Reprint requests: Leonoor I. Los, MD, PhD, Department of Ophthalmology, University Medical Center Groningen, BB 61, P.O. Box 30.001, 9700 RB Groningen, the Netherlands; e-mail: firstname.lastname@example.org
Supported by Stichting Blindenhulp (Blind Aid Foundation), the Netherlands.
None of the authors have any conflicting interests to disclose.