Involvement of Anoikis in Dissociated Optic Nerve Fiber Layer Appearance

Abstract

Dissociated optic nerve fiber layer (DONFL) appearance is characterized by dimpling of the fundus when observed after vitrectomy with the internal limiting membrane (ILM) peeling in macular diseases. However, the cause of DONFL remains largely unknown. Optical coherence tomography (OCT) findings have indicated that the nerve fiber layer (NFL) and ganglion cells are likely to have been damaged in patients with DONFL appearance. Since DONFL appearance occurs at a certain postoperative period, it is unlikely to be retinal damage directly caused by ILM peeling because apoptosis occurs at a certain period after tissue damage and/or injury. However, it may be due to ILM peeling-induced apoptosis in the retinal tissue. Anoikis is a type of apoptosis that occurs in anchorage-dependent cells upon detachment of those cells from the surrounding extracellular matrix (i.e., the loss of cell anchorage). The anoikis-related proteins βA3/A1 crystallin and E-cadherin are reportedly expressed in retinal ganglion cells. Thus, we theorize that one possible cause of DONFL appearance is ILM peeling-induced anoikis in retinal ganglion cells.

Internal Limiting Membrane Peeling Distorts the Retinal Layers and Induces Scotoma Formation in the Perifoveal Temporal Macula

“…An indirect effect may involve these cells undergoing anoikis, a kind of apoptosis that occurs when anchorage-dependent cells detach from the surrounding extracellular matrix (i.e., the loss of cell anchorage). 30 The resulting void exposes the ONL to contractility of the residual ILM, which pulls it upward to the vitreoretinal interface. These events disrupt the visual signal processing pathway, resulting in scotomas onset.…”

Analysis of Retinal Microstructure in Eyes with Dissociated Optic Nerve Fiber Layer (DONFL) Appearance following Idiopathic Macular Hole Surgery: An Optical Coherence Tomography Study

“…Another hypothesis in the pathogenesis of DONFL is related to anoikis in RGCs [ 28 ]. Anchorage-dependent cells that undergo dissociation from the surrounding extracellular matrix experience a type of apoptosis known as anoikis [ 29 ].…”

Long-Term Quantitative Analysis of Inner Retinal Dimples and Visual Function Post Internal Limiting Membrane Peeling in Macular Diseases

“…Being interposed by neurons and photoreceptors, Müller cells participate in light transmitting through endfeet to main process as “optical fiber” and lend support to surrounding microenvironment functionally and metabolically [ 16 , 21 , 30 ]. ILM peeling might damage the endfoot of Müller cells, hampering the microenvironment of RGCs, causing anoikis and eventually leading to the loss of visual function [ 31 – 33 ]. To support this, Akino et al.…”