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.

Keywords: E-cadherin; anoikis; dissociated optic nerve fiber layer (DONFL); internal limiting membrane (ILM); macular hole (MH); optical coherence tomography (OCT); retinal ganglion cell; vitrectomy; βA3/A1 crystallin.

Figure 1

Fundus photograph of a patient obtained pre (A) and post (B) vitrectomy surgery for an idiopathic macular hole (MH). Ophthalmoscopically, the dissociated optic nerve fiber layer (DONFL) appearance features arcuate striae color changes, which appear to be multilinear shaped, that are frequently observed in the macular nerve fiber layer ((B), white arrowheads).

Figure 2

Optical coherence tomography (OCT) images of a patient with an idiopathic macular hole (MH) obtained pre-surgery (A) and at 6-months postoperative (B). OCT scans frequently showed thinning and irregularity of the inner retinal layer ((B), black arrowheads), thus indicating that the nerve fiber layer and ganglion cells were highly likely to have been damaged. The patient’s visual acuity was 20/100 before surgery and 20/25 after surgery.

Figure 3

Immunostaining for Ki67 of Monkey Foveal Retina (cited from Reference [77]); (A) Scattered Ki67-positive spots (red) are visible in the innermost retinal layer in the parafoveola (white arrowheads). Moreover, some parts of the region believed to be the inner granular layer are also positive (unfilled arrowheads); (B) Immunostaining for Ki67 includes the immunostaining for DAPI (blue).