Immunohistochemical, Functional, and Anatomical Evaluation of Patients with Idiopathic Epiretinal Membrane

Overview

Journal Graefes Arch Clin Exp Ophthalmol

Specialty Ophthalmology

Date 2024 Jan 10

PMID 38197992

Authors

Julio Cesar Molina Martin

Laura Fernandez Sanchez

David P Pinero

Nicolas Cuenca Navarro

Affiliations

Soon will be listed here.

Abstract

Purpose: The main purpose of this study was to perform an immunohistochemical, functional, and anatomical evaluation of patients with idiopathic epiretinal membrane (ERM).

Methods: Twenty-four specimens of idiopathic ERM from 24 consecutive patients who underwent 23 G pars plana vitrectomy for ERM and internal limiting membrane (ILM) peeling at the San Juan University Hospital in Alicante (Spain) in 2019 were analyzed. All patients underwent a complete ophthalmological examination including measurement of best corrected visual acuity (BCVA) and macular analysis by spectral-domain optical coherence tomography (SD-OCT) at the time of diagnosis and 3 months after surgery. Specific glial fibrillar acid protein antibodies (GFAP) and S100 calcium-binding protein β (S100β) immunostaining markers were used to identify the macroglial component of the ERM, Müller cells, and astrocytes. Ionized calcium-binding adapter molecule 1 protein (Iba1) antibodies were used as specific markers for inflammatory cells, such as microglia and macrophages.

Results: Mean preoperative BCVA measured with Snellen chart was 0.3 and 0.6 preoperatively and at 3 months after surgery, respectively. SD-OCT identified 15 patients (62.5%) with a disruption of the outer retinal hyperreflective bands. The immunohistochemical study showed the presence of Müller cells in almost all cases (91.6%), as well of abundant microglia and macrophages. Microglia and macrophages were more frequently present in earlier stages of ERM. Microglia were present in ERM independently of the outer retinal hyperreflective bands integrity as measured by SD-OCT. A greater presence of macrophages was found in those ERMs with no outer retinal hyperreflective band disruption.

Conclusions: Müller cells seem to be the most frequent cell group in ERMs, with also presence of microglia cells and macrophages. Astrocytes were more frequently found in early stages of ERMs. Microglia and macrophages were most frequent in ERMs with early stage (1, 2, or 3) than in advanced stages (4).

References

Schumann R, Eibl K, Zhao F, Scheerbaum M, Scheler R, Schaumberger M . Immunocytochemical and ultrastructural evidence of glial cells and hyalocytes in internal limiting membrane specimens of idiopathic macular holes. Invest Ophthalmol Vis Sci. 2011; 52(11):7822-34. DOI: 10.1167/iovs.11-7514. View

FOOS R . Vitreoretinal juncture--simple epiretinal membranes. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1974; 189(4):231-50. DOI: 10.1007/BF02384852. View

Grossmann R, Stence N, Carr J, Fuller L, Waite M, Dailey M . Juxtavascular microglia migrate along brain microvessels following activation during early postnatal development. Glia. 2002; 37(3):229-40. View

Provis J, Penfold P, Edwards A, Van Driel D . Human retinal microglia: expression of immune markers and relationship to the glia limitans. Glia. 1995; 14(4):243-56. DOI: 10.1002/glia.440140402. View

Kase S, Saito W, Yokoi M, Yoshida K, Furudate N, Muramatsu M . Expression of glutamine synthetase and cell proliferation in human idiopathic epiretinal membrane. Br J Ophthalmol. 2005; 90(1):96-8. PMC: 1856891. DOI: 10.1136/bjo.2005.078394. View

Miguel A, Legris A . Prognostic factors of epiretinal membranes: A systematic review. J Fr Ophtalmol. 2017; 40(1):61-79. DOI: 10.1016/j.jfo.2016.12.001. View

Dawson S, Shunmugam M, Williamson T . Visual acuity outcomes following surgery for idiopathic epiretinal membrane: an analysis of data from 2001 to 2011. Eye (Lond). 2013; 28(2):219-24. PMC: 3930265. DOI: 10.1038/eye.2013.253. View

Lesnik Oberstein S, Byun J, Herrera D, Chapin E, Fisher S, Lewis G . Cell proliferation in human epiretinal membranes: characterization of cell types and correlation with disease condition and duration. Mol Vis. 2011; 17:1794-805. PMC: 3133557. View

Ozog M, Nowak-Was M, Rokicki W . Pathophysiology and clinical aspects of epiretinal membrane - review. Front Med (Lausanne). 2023; 10:1121270. PMC: 10447902. DOI: 10.3389/fmed.2023.1121270. View

10.

Fischer A, Zelinka C, Scott M . Heterogeneity of glia in the retina and optic nerve of birds and mammals. PLoS One. 2010; 5(6):e10774. PMC: 2887354. DOI: 10.1371/journal.pone.0010774. View

11.

Coltrini D, Belleri M, Gambicorti E, Romano D, Morescalchi F, Krishna Chandran A . Gene expression analysis identifies two distinct molecular clusters of idiopatic epiretinal membranes. Biochim Biophys Acta Mol Basis Dis. 2020; 1866(12):165938. DOI: 10.1016/j.bbadis.2020.165938. View

12.

Govetto A, Lalane 3rd R, Sarraf D, Figueroa M, Hubschman J . Insights Into Epiretinal Membranes: Presence of Ectopic Inner Foveal Layers and a New Optical Coherence Tomography Staging Scheme. Am J Ophthalmol. 2016; 175:99-113. DOI: 10.1016/j.ajo.2016.12.006. View

13.

Cuenca N, Ortuno-Lizaran I, Pinilla I . Cellular Characterization of OCT and Outer Retinal Bands Using Specific Immunohistochemistry Markers and Clinical Implications. Ophthalmology. 2017; 125(3):407-422. DOI: 10.1016/j.ophtha.2017.09.016. View

14.

Zayas-Santiago A, Agte S, Rivera Y, Benedikt J, Ulbricht E, Karl A . Unidirectional photoreceptor-to-Müller glia coupling and unique K+ channel expression in Caiman retina. PLoS One. 2014; 9(5):e97155. PMC: 4022631. DOI: 10.1371/journal.pone.0097155. View

15.

da Silva R, Roda V, Matsuda M, Siqueira P, Lustoza-Costa G, Wu D . Cellular components of the idiopathic epiretinal membrane. Graefes Arch Clin Exp Ophthalmol. 2021; 260(5):1435-1444. DOI: 10.1007/s00417-021-05492-7. View

16.

Ashwell K, Hollander H, Streit W, Stone J . The appearance and distribution of microglia in the developing retina of the rat. Vis Neurosci. 1989; 2(5):437-48. DOI: 10.1017/s0952523800012335. View

17.

Fung A, Galvin J, Tran T . Epiretinal membrane: A review. Clin Exp Ophthalmol. 2021; 49(3):289-308. DOI: 10.1111/ceo.13914. View

18.

Vinores S, Campochiaro P, Conway B . Ultrastructural and electron-immunocytochemical characterization of cells in epiretinal membranes. Invest Ophthalmol Vis Sci. 1990; 31(1):14-28. View

19.

Provis J, Diaz C, Penfold P . Microglia in human retina: a heterogeneous population with distinct ontogenies. Perspect Dev Neurobiol. 1996; 3(3):213-22. View

20.

Bu S, Kuijer R, Van der Worp R, Postma G, Renardel de Lavalette V, Li X . Immunohistochemical Evaluation of Idiopathic Epiretinal Membranes and In Vitro Studies on the Effect of TGF-β on Müller Cells. Invest Ophthalmol Vis Sci. 2015; 56(11):6506-14. DOI: 10.1167/iovs.14-15971. View