A Positive Association Between Intrinsically Photosensitive Retinal Ganglion Cells and Retinal Nerve Fiber Layer Thinning in Glaucoma

AbstractThe organization of the primate nerve fiber layer and optic nerve head with respect to the positioning of central and peripheral axons remains controversial. Data were obtained from 32 human fetal retinae aged between 15 and 21 weeks of gestation. Crystals of the carbocyanine dyes, DiI or DiA, and fluorescence microscopy were used to identify axonal populations from peripheral retinal ganglion cells. Peripheral ganglion cell axons were scattered throughout the vitreal-scleral depth of the nerve fiber layer. Such a scattered distribution was maintained as the fibers passed through the optic nerve head and along the optic nerve. There was a rough topographic representation within the optic nerve head according to retinal quadrant such that both peripheral and central fibers were mixed within a wedge extending from the periphery to the center of the nerve. There was no indication that the fibers were reorganized in any way as they passed through the optic disc and into the nerve. The present results suggest that any degree of order present within the fiber layer and optic nerve is not an active process but a passive consequence of combining the fascicles of the retinal nerve fiber layer. Optic axons are not instructed to establish a retinotopic order and the effect of guidance cues in reordering fibers, particularly evident prechiasmatically and postchiasmatically, does not appear to be present within the nerve fiber layer or optic nerve head in humans.

Download Full-text

Estimated Retinal Ganglion Cell Counts in Glaucomatous Eyes with Localized Retinal Nerve Fiber Layer Defects

American Journal of Ophthalmology ◽

10.1016/j.ajo.2013.04.015 ◽

2013 ◽

Vol 156 (3) ◽

pp. 578-587.e1 ◽

Cited By ~ 20

Author(s):

Andrew J. Tatham ◽

Robert N. Weinreb ◽

Linda M. Zangwill ◽

Jeffrey M. Liebmann ◽

Christopher A. Girkin ◽

...

Keyword(s):

Ganglion Cell ◽

Nerve Fiber ◽

Retinal Ganglion Cell ◽

Retinal Nerve Fiber Layer ◽

Retinal Ganglion ◽

Fiber Layer ◽

Nerve Fiber Layer ◽

Cell Counts ◽

Retinal Nerve Fiber

Download Full-text

Longitudinal changes in superficial microvasculature in glaucomatous retinal nerve fiber layer defects after disc hemorrhage

Scientific Reports ◽

10.1038/s41598-020-79151-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Yoko Okamoto ◽

Tadamichi Akagi ◽

Kenji Suda ◽

Takanori Kameda ◽

Masahiro Miyake ◽

...

Keyword(s):

Nerve Fiber ◽

Retinal Nerve Fiber Layer ◽

Ganglion Cells ◽

Fiber Layer ◽

Disc Hemorrhage ◽

Longitudinal Changes ◽

Nerve Fiber Layer ◽

Subsequent Decrease ◽

Retinal Microvasculature ◽

Retinal Nerve Fiber

AbstractGlaucoma is a multifactorial optic neuropathy, possibly involving vascular dysfunction, leading to the death of retinal ganglion cells and their axons. Disc hemorrhage (DH) is known to be closely associated with the widening of retinal nerve fiber layer defect (NFLD); however, it has not been well elucidated how DH affects retinal microvasculature. We aimed to investigate the association between DH history and longitudinal changes in superficial retinal microvasculature in NFLD. We enrolled 15 glaucoma patients with DH history (32 glaucomatous NFLD locations, with or without DH history). NFLD-angle, superficial retinal vessel density (VD), and decreased superficial retinal microvasculature (deMv)-angle were assessed using optical coherence tomography angiography for at least three times over time. The mean follow-up period and OCT/OCTA scan interval were 21.3 ± 5.4 months (range, 12–28) and 6.8 ± 0.4 months (range, 2–18), respectively. Linear mixed-effects models showed that the presence of DH history was significantly associated with an additional NFLD-angle widening of 2.19 degree/year (P = 0.030), VD decrease of 1.88%/year (P = 0.015), and deMv-angle widening of 3.78 degree/year (P < 0.001). These changes were significantly correlated with each other (P < 0.001). Thus, the widening of NFLD was closely associated with deMv, and DH was associated with a subsequent decrease in superficial retinal microvasculature in NFLD.

Download Full-text

Involvement of Anoikis in Dissociated Optic Nerve Fiber Layer Appearance

International Journal of Molecular Sciences ◽

10.3390/ijms22041724 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1724

Author(s):

Tsunehiko Ikeda ◽

Kimitoshi Nakamura ◽

Takaki Sato ◽

Teruyo Kida ◽

Hidehiro Oku

Keyword(s):

Optic Nerve ◽

Nerve Fiber ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Internal Limiting Membrane ◽

Retinal Ganglion ◽

Ilm Peeling ◽

Fiber Layer ◽

Nerve Fiber Layer ◽

Optic Nerve Fiber

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.

Download Full-text

Minimizing activation of overlying axons with epiretinal stimulation: The role of fiber orientation and electrode configuration

10.1101/245266 ◽

2018 ◽

Cited By ~ 1

Author(s):

Timothy Esler ◽

Robert R. Kerr ◽

Bahman Tahayori ◽

David B. Grayden ◽

Hamish Meffin ◽

...

Keyword(s):

Ganglion Cell ◽

Nerve Fiber ◽

Retinal Ganglion Cells ◽

Ganglion Cell Layer ◽

Ganglion Cells ◽

Cell Layer ◽

Retinal Ganglion ◽

Fiber Layer ◽

Nerve Fiber Layer ◽

Stimulation Of

ABSTRACTObjective. Currently, a challenge in electrical stimulation of the retina is to excite only the cells lying directly under the electrode in the ganglion cell layer, while avoiding excitation of the axons that pass over the surface of the retina in the nerve fiber layer. Since these passing fibers may originate from distant regions of the ganglion cell layer. Stimulation of both target retinal ganglion cells and overlying axons results in irregular visual percepts, significantly limiting perceptual efficacy. This research explores how differences in fiber orientation between the nerve fiber layer and ganglion cell layer leads to differences in the activation of the axon initial segment and axons of passage. Approach. Axons of passage of retinal ganglion cells in the nerve fiber layer are characterized by a narrow distribution of fiber orientations, causing highly anisotropic spread of applied current. In contrast, proximal axons in the ganglion cell layer have a wider distribution of orientations. A four-layer computational model of epiretinal extracellular stimulation that captures the effect of neurite orientation in anisotropic tissue has been developed using a modified version of the standard volume conductor model, known as the cellular composite model. Simulations are conducted to investigate the interaction of neural tissue orientation, stimulating electrode configuration, and stimulation pulse duration and amplitude. Main results. The dependence of fiber activation on the anisotropic nature of the nerve fiber layer is first established. Via a comprehensive search of key parameters, our model shows that the simultaneous stimulation with multiple electrodes aligned with the nerve fiber layer can be used to achieve selective activation of axon initial segments rather than passing fibers. This result can be achieved with only a slight increase in total stimulus current and modest increases in the spread of activation in the ganglion cell layer, and is shown to extend to the general case of arbitrary electrode array positioning and arbitrary target neural volume. Significance. These results elucidate a strategy for more targeted stimulation of retinal ganglion cells with experimentally-relevant multi-electrode geometries and readily achievable stimulation requirements.

Download Full-text