Abstract

Aging is a phenomenon that is associated with profound medical implications. Idiopathic epiretinal membrane (iEMR) and macular hole (MH) are the major vision‐threatening vitreoretinal diseases affecting millions of aging people globally, making these conditions an important public health issue. iERM is characterized by fibrous tissue developing on the surface of the macula, which leads to biomechanical and biochemical macular damage. MH is a small breakage in the macula and is associated with many ocular conditions. Although several individual factors and pathways are suggested, a systems pathology level understanding of the molecular mechanisms underlying these disorders is lacking. Therefore, we performed mass spectrometry‐based label‐free quantitative proteomics analysis of the vitreous proteomes from patients with iERM and MH to identify the key proteins, as well as the multiple interconnected biochemical pathways, contributing to the development of these diseases. We identified a total of 1,014 unique proteins, many of which are linked to inflammation and the complement cascade, revealing the inflammation processes in retinal diseases. Additionally, we detected a profound difference in the proteomes of iEMR and MH compared to those of diabetic retinopathy with macular edema and rhegmatogenous retinal detachment. A large number of neuronal proteins were present at higher levels in the iERM and MH vitreous, including neuronal adhesion molecules, nervous system development proteins, and signaling molecules, pointing toward the important role of neurodegenerative component in the pathogenesis of age‐related vitreoretinal diseases. Despite them having marked similarities, several unique vitreous proteins were identified in both iERM and MH, from which candidate targets for new diagnostic and therapeutic approaches can be provided.

Highlights

  • IntroductionTissue dysfunction associated with aging affects all vital organs, including the eyes

  • Population aging is a global phenomenon with profound medical implications

  • 2.1 | Study plan and the patients’ preoperative analyses. Both iERM and macular hole (MH) patients have similar visual disturbances and symptoms, including metamorphopsia, photopsia, blurred vision, and decreased visual acuity, these are different pathological conditions. iERM presents with a thin layer of scar tissue that forms on the posterior pole of the human anatomic macula, whereas MH manifests as a partial or full‐thickness loss of tissue in the central retina (Figure 1a)

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Summary

Introduction

Tissue dysfunction associated with aging affects all vital organs, including the eyes. Idiopathic epiretinal membrane (iEMR) and macular hole (MH) are the major vision‐threatening vitreoretinal interface diseases that affect millions of aging people globally, making these conditions an important public health issue (Steel & Lotery, 2013). IERM is characterized by the growth of fibrocellular tissue along the inner surface of the retina (Snead, James, & Snead, 2008). An impaired repair and an excess of fibrosis in iERM eyes lead to biomechanical and biochemical macular damage, the development of retinal surface wrinkling with or without shallow tractional retinal detachment (RD), macular vascular distortion, the breakdown of the blood–retinal barrier at the retinal pigment epithelial (RPE) level, and vascular leakage. MH was described in the trauma setting, but it has been associated with many ocular conditions, and the greater majority of MH cases are idiopathic (Chung & Byeon, 2017)

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