scholarly journals Local Accumulation of Axonal Mitochondria in the Optic Nerve Glial Lamina Precedes Myelination

2021 ◽  
Author(s):  
Samantha J. Wilkison ◽  
Cora L. Bright ◽  
Ricardo Vancini ◽  
Daniel J. Song ◽  
Howard M. Bomze ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Energy Requirement ◽  
Lamina Cribrosa ◽  
High Density ◽  
Retinal Ganglion ◽  
Unmyelinated Axons ◽  
Local Functions ◽  
New Research ◽  
Local Accumulation

AbstractMitochondria are essential for neurons and must be optimally distributed along their axon to fulfil local functions. A high density of mitochondria has been observed in retinal ganglion cell (RGC) axons of an unmyelinated region of the optic nerve, called the glial lamina (GL) in mouse (lamina cribrosa in human). In glaucoma, the world’s leading cause of irreversible blindness, the GL is the epicenter of RGC degeneration and is connected to mitochondrial dysfunction. It is generally accepted that the local accumulation of mitochondria in the GL is established due to the higher energy requirement of unmyelinated axons. Here we revisit the connection between mitochondrial positioning and myelin in RGC axons. We show that the high density of mitochondria in the GL is restricted to larger axons and is established before myelination. Thus, contrary to a longstanding belief in the field, the myelination pattern is not responsible for the establishment of the local accumulation of mitochondria in GL axons. Our findings open new research avenues likely critical to understanding the pathophysiology of glaucoma.

scholarly journals Local Accumulation of Axonal Mitochondria in the Optic Nerve Glial Lamina Precedes Myelination

2021 ◽  
Vol 15 ◽  
Author(s):  
Samantha J. Wilkison ◽  
Cora L. Bright ◽  
Ricardo Vancini ◽  
Daniel J. Song ◽  
Howard M. Bomze ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Energy Requirement ◽  
Lamina Cribrosa ◽  
High Density ◽  
Retinal Ganglion ◽  
Unmyelinated Axons ◽  
Local Functions ◽  
New Research ◽  
Local Accumulation

Mitochondria are essential for neurons and must be optimally distributed along their axon to fulfill local functions. A high density of mitochondria has been observed in retinal ganglion cell (RGC) axons of an unmyelinated region of the optic nerve, called the glial lamina (GL) in mouse (lamina cribrosa in human). In glaucoma, the world's leading cause of irreversible blindness, the GL is the epicenter of RGC degeneration and is connected to mitochondrial dysfunction. It is generally accepted that the local accumulation of mitochondria in the GL is established due to the higher energy requirement of unmyelinated axons. Here we revisit the connection between mitochondrial positioning and myelin in RGC axons. We show that the high density of mitochondria in the GL is restricted to larger axons and is established before myelination. Thus, contrary to a longstanding belief in the field, the myelination pattern is not responsible for the establishment of the local accumulation of mitochondria in GL axons. Our findings open new research avenues likely critical to understanding the pathophysiology of glaucoma.

Scleral Biomechanics in the Glaucomatous Monkey Eye

2009 ◽  
Author(s):  
Michaël J. A. Girard ◽  
Jun-Kyo F. Suh ◽  
Michael Bottlang ◽  
Claude F. Burgoyne ◽  
J. Crawford Downs
Keyword(s):  
Intraocular Pressure ◽  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Nutritional Support ◽  
Lamina Cribrosa ◽  
Collagen Fibers ◽  
Type I ◽  
Retinal Ganglion ◽  
The Brain

The sclera is the outer shell and principal load-bearing tissue of the eye, and consists primarily of avascular lamellae of collagen fibers. Ninety percent of the collagen fibers in the sclera are Type I, which provide the eye with necessary mechanical strength to withstand intraocular pressure (IOP). A small hole pierces the posterior sclera, known as the scleral canal, through which the retinal ganglion cell axons turn and pass out of the eye on their path to the brain. The scleral canal is spanned by a fenestrated connective tissue called the lamina cribrosa that provides structural and nutritional support to the axons as they leave the eye. This region, including the peripapillary sclera (the sclera closest to the canal), the lamina cribrosa, and the contained retinal ganglion cell axons, is collectively known as the optic nerve head or ONH.

scholarly journals Translational profiling of retinal ganglion cell optic nerve regeneration in Xenopus laevis

2017 ◽  
Vol 426 (2) ◽  
pp. 360-373 ◽  
Author(s):  
G.B. Whitworth ◽  
B.C. Misaghi ◽  
D.M. Rosenthal ◽  
E.A. Mills ◽  
D.J. Heinen ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Xenopus Laevis ◽  
Ganglion Cell ◽  
Nerve Regeneration ◽  
Retinal Ganglion Cell ◽  
Retinal Ganglion ◽  
Optic Nerve Regeneration

Different functional susceptibilities of mouse retinal ganglion cell subtypes to optic nerve crush injury

2017 ◽  
Vol 162 ◽  
pp. 97-103 ◽  
Author(s):  
Zhen Puyang ◽  
Hai-Qing Gong ◽  
Shi-Gang He ◽  
John B. Troy ◽  
Xiaorong Liu ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Crush Injury ◽  
Optic Nerve Crush ◽  
Retinal Ganglion ◽  
Nerve Crush ◽  
Nerve Crush Injury

scholarly journals Microvascular Density Is Associated With Retinal Ganglion Cell Axonal Volume in the Laminar Compartments of the Human Optic Nerve Head

2018 ◽  
Vol 59 (3) ◽  
pp. 1562 ◽  
Author(s):  
Min H. Kang ◽  
Mengchen Suo ◽  
Chandrakumar Balaratnasingam ◽  
Paula K. Yu ◽  
William H. Morgan ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Optic Nerve Head ◽  
Microvascular Density ◽  
Retinal Ganglion ◽  
Human Optic Nerve

Long-Term Effect of Optic Nerve Axotomy on the Retinal Ganglion Cell Layer

2015 ◽  
Vol 56 (10) ◽  
pp. 6095 ◽  
Author(s):  
Francisco M. Nadal-Nicolás ◽  
Paloma Sobrado-Calvo ◽  
Manuel Jiménez-López ◽  
Manuel Vidal-Sanz ◽  
Marta Agudo-Barriuso
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Ganglion Cell Layer ◽  
Cell Layer ◽  
Term Effect ◽  
Retinal Ganglion ◽  
Long Term Effect ◽  
Retinal Ganglion Cell Layer

scholarly journals Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma

2007 ◽  
Vol 179 (7) ◽  
pp. 1523-1537 ◽  
Author(s):  
Gareth R. Howell ◽  
Richard T. Libby ◽  
Tatjana C. Jakobs ◽  
Richard S. Smith ◽  
F. Campbell Phalan ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Mouse Model ◽  
Retinal Ganglion Cells ◽  
Strong Evidence ◽  
Ganglion Cells ◽  
Lamina Cribrosa ◽  
Retinal Ganglion ◽  
Rich Region ◽  
Pattern Electroretinography ◽  
Axon Damage

Here, we use a mouse model (DBA/2J) to readdress the location of insult(s) to retinal ganglion cells (RGCs) in glaucoma. We localize an early sign of axon damage to an astrocyte-rich region of the optic nerve just posterior to the retina, analogous to the lamina cribrosa. In this region, a network of astrocytes associates intimately with RGC axons. Using BAX-deficient DBA/2J mice, which retain all of their RGCs, we provide experimental evidence for an insult within or very close to the lamina in the optic nerve. We show that proximal axon segments attached to their cell bodies survive to the proximity of the lamina. In contrast, axon segments in the lamina and behind the eye degenerate. Finally, the Wlds allele, which is known to protect against insults to axons, strongly protects against DBA/2J glaucoma and preserves RGC activity as measured by pattern electroretinography. These experiments provide strong evidence for a local insult to axons in the optic nerve.

scholarly journals Exosome-Mediated Delivery of the Neuroprotective Peptide PACAP38 Promotes Retinal Ganglion Cell Survival and Axon Regeneration in Rats With Traumatic Optic Neuropathy

2021 ◽  
Vol 9 ◽  
Author(s):  
Tian Wang ◽  
Yiming Li ◽  
Miao Guo ◽  
Xue Dong ◽  
Mengyu Liao ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Optic Neuropathy ◽  
Axon Regeneration ◽  
Retinal Ganglion ◽  
Traumatic Optic Neuropathy ◽  
Fiber Layer

Traumatic optic neuropathy (TON) refers to optic nerve damage caused by trauma, leading to partial or complete loss of vision. The primary treatment options, such as hormonal therapy and surgery, have limited efficacy. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), a functional endogenous neuroprotective peptide, has emerged as a promising therapeutic agent. In this study, we used rat retinal ganglion cell (RGC) exosomes as nanosized vesicles for the delivery of PACAP38 loaded via the exosomal anchor peptide CP05 (EXOPACAP38). EXOPACAP38 showed greater uptake efficiency in vitro and in vivo than PACAP38. The results showed that EXOPACAP38 significantly enhanced the RGC survival rate and retinal nerve fiber layer thickness in a rat TON model. Moreover, EXOPACAP38 significantly promoted axon regeneration and optic nerve function after injury. These findings indicate that EXOPACAP38 can be used as a treatment option and may have therapeutic implications for patients with TON.

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