 |
|
The Distribution of Mitochondrial Activity in Relation to Optic Nerve Structure
Elizabeth A. Bristow, FRCOphth;
Philip G. Griffiths, FRCOphth;
Richard M. Andrews, PhD, FRCOphth;
Margaret A. Johnson, PhD;
Douglas M. Turnbull, PhD, FRCP
Arch Ophthalmol. 2002;120:791-796.
ABSTRACT
| |
Background The observation of a buildup of mitochondria at
the level of the lamina cribrosa in the optic nerve head has
traditionally been attributed to axoplasmic stasis. However, this
region is also the transition zone for myelination, resulting in
differing energy requirements.
Objective To investigate the relationship between
myelination and mitochondrial activity in optic nerve
tissue.
Methods Histological, histochemical, and immunocytochemical
techniques were used to demonstrate the distribution of myelin,
cytochrome-c oxidase activity, and laminar structure in human
optic nerve tissue. A study of rabbit optic nerve and retina and
unmyelinated human pituitary stalk was also performed.
Cytochrome-c oxidase activity in the human optic nerve tissue
was measured using microphotometry.
Results There was a striking inverse relationship between
myelination and mitochondrial distribution in all tissue studied.
Statistical analysis of microphotometric data showed this distribution
to be highly significant.
Conclusion We caution against the previous inference of
a process of axoplasmic stasis and suggest that, instead, the
distribution of mitochondria reflects the functional requirement of
different regions of the ganglion cell axon.
Clinical Relevance Optic neuropathy is associated with several
inherited disorders of mitochondria. We suggest that a fine balance
exists between energy demand and tissue function in the optic nerve,
which may explain why optic nerve pathological features are seen in
those with mitochondrial disease.
INTRODUCTION
THE OPTIC nerve is an
extension of the central nervous system with unique structural
features. Unmyelinated nerve fibers exit the eye through the lamina
cribrosa, becoming myelinated at the posterior border. At the
ultrastructural level, the concentration of mitochondria decreases
dramatically at the level of the lamina. The finding of increased
numbers of mitochondria in the prelaminar and laminar regions of the
optic nerve has traditionally been attributed to mechanical
constriction or axoplasmic stasis at the lamina.1-4 This,
in turn, has influenced our investigation and understanding of optic
neuropathies, such as Leber hereditary optic neuropathy and glaucoma,
but leaves many unanswered questions.
We suggest that mitochondrial distribution has little to do with
the laminar structure, but rather reflects a functional requirement of
this highly specialized tissue, as myelinated and unmyelinated fibers
have different bioenergetic properties.
In this study, we sought to relate the differences in mitochondrial
enzyme activity to the distribution of myelination. In addition to
normal human optic nerve, we studied pig optic nerve, which is
structurally similar to the human, and rabbit optic nerve, which has
important differences. In contrast to human and pig optic nerve, the
rabbit has no well-ordered laminar structure and the entire optic nerve
is myelinated.
Myelination continues onto the retina in a horizontal
band.5 This provides an opportunity not only to look at
mitochondrial enzyme activity in the myelinated optic nerve but also to
observe what happens at the myelination/demyelination interface on the
retina. We also studied human pituitary stalk nerve fibers, as these
are one of few examples of other unmyelinated tissue within the central
nervous system.
MATERIALS AND METHODS
MATERIALS AND PREPARATION
Following approval by the local research ethics committee,
postmortem human optic nerve tissue was obtained from 8 corneal donors,
aged 22 to 84 years, with no history of ocular or mitochondrial
disease. Once the corneal scleral disc was removed and placed in
transport medium (Optisol GS; Chiron Intraoptics, Irvine, Calif) for
transfer to one of the national eye banks, the optic nerve was removed
from the globe with a small surrounding collar of retina. Specimens
were mounted on gelatin blocks and rapidly frozen in isopentane and
liquid nitrogen before storing at -80°C.
Pig optic nerve tissue was prepared in a similar fashion, while rabbit
globes were frozen whole before dissection to maintain the fragile
retinal nerve fiber layer. All animal tissue was harvested postmortem,
and care and housing conformed to codes of practice under the
Prevention of Cruelty to Animals Act 1986 (part 3, scientific
procedures).
The postmortem time for human optic nerve ranged from 3 to 22 hours;
for pig, 3 to 6 hours; and for rabbit, 20 to 60 minutes. A sample of
pituitary stalk tissue (35 hours post mortem) had been snap frozen and
stored at -80°C.
Sections (10 µm thick) were cut using a cryostat microtome (model
2800N Frigocut; Reichert Ophthalmic Instruments, Depew, NY).
Longitudinal and transverse sections of the optic nerve were studied.
HISTOLOGICAL METHODS
Sudan black B fat staining was used to demonstrate myelination,
and hematoxylin-eosin staining was used to confirm good tissue
preservation. Histochemical localization of cytochrome-c
oxidase activity was performed by incubating sections at 38°C for 1
hour in a combination of 4mM 3,3'-diaminobenzidine hydrochloride and
100µM cytochrome c in 0.1M phosphate buffer (pH,
7.0).6 A mouse monoclonal antibody to
cytochrome-c oxidase subunit II was used in a 1:500 dilution
to confirm the distribution of cytochrome-c oxidase components
in human tissue. The technique used has been previously
described.7 The lamina cribrosa structure was demonstrated
using mouse monoclonal laminin antibodies  5 (1 in 100), 2 (1 in
100),  1 (1 in 100), and  1 (1 in 1000) (Chemicon International,
Inc, Temecula, Calif). Sections were air dried for 1 hour
before application of the primary antibody and incubation for 1 hour at
room temperature. Sections were then washed in 0.0125M
phosphate-buffered saline for 30 minutes and incubated for 1 hour with
rabbit anti–mouse peroxidase conjugate (1 in 100; Dako, Glostrup,
Denmark). Following further washes in phosphate-buffered
saline for 30 minutes, the sections were developed in 0.05%
3,3'-diaminobenzidine and 0.01% hydrogen peroxide for 15 minutes. The
neurofilament antibody SMI 31 (1 in 200; Affiniti Research Products
Ltd, Exeter, England) was used to confirm the presence of nerve fiber
tissue in sections of pituitary stalk. The same secondary antibody
labeling method as previously described was used.
Sections of normal striate muscle were used for controls. Retinal
tissue surrounding the optic nerve in all sections also served as
an internal control for cytochrome-c oxidase studies, because
the outer segment of photoreceptors has high
cytochrome-c oxidase activity.
QUANTIFICATION
Seven 10-µm longitudinal sections of human optic nerve, taken from 2
individuals, were used. Following histochemical demonstration of
cytochrome-c oxidase activity, the images were
divided into columns of 20 points, separated by approximately 100 µm.
A total of 1195 points were sampled using a microphotometer (Universal
Microphotometer System, model 30; Carl Zeiss, Göttingen, Germany)
with a computer-controlled scanning stage.
RESULTS
We confirmed that there is a striking inverse relationship between
cytochrome-c oxidase activity and myelination following
observation of longitudinal (Figure
1) and transverse (Figure
2) sections of the
normal human optic nerve.6, 8 This
finding is most clearly demonstrated in serial transverse sections
because it is easier to define the posterior limit of the lamina
cribrosa in this plane. The posterior limit of the lamina is often
closely associated with the onset of myelination; however, there are
small variations across the optic nerve head in some individuals and,
in these cases, the cytochrome-c oxidase activity seems to
correlate with the myelination pattern rather than with the laminar
structure.
|
|
|
|
Figure 1. Human optic nerve in transverse section.
A, Sudan black B fat staining
shows myelination. B, Cytochrome-c oxidase: histochemical
demonstration that activity is relatively high in unmyelinated regions of the optic nerve.
Original magnification x40 for both
illustrations.
|
|
|
|
|
|
|
Figure 2.
Serial sections of the human optic nerve in cross section. A, Sudan
black B fat staining shows myelination. B, Immunocytochemical
labeling
for laminin to demonstrate the posterior laminar position.
C, Cytochrome-c oxidase histochemistry demonstrating
relatively high levels of activity
in unmyelinated regions. D,
Immunocytochemical labeling of the cytochrome-c oxidase
subunit II monoclonal antibody showing a similar distribution
to that shown by cytochrome-c
oxidase histochemistry. Original
magnification x40 for all illustrations.
|
|
|
Figure 2 shows one such example, where myelination does not reach the
lamina in the central optic nerve region. Immunocytochemistry using the
cytochrome-c
oxidase subunit II antibody conforms to the same
pattern, showing that the high cytochrome-c oxidase
activity in unmyelinated regions is a result of an increased
concentration of respiratory chain components.
We quantified the variation in cytochrome-c oxidase activity
across the human optic nerve head. Microphotometric analysis shows that
the difference in cytochrome-c oxidase activity between
prelaminar and laminar regions when compared with the postlaminar optic
nerve is highly statistically significant in all sections studied. A
t test comparing the cytochrome-c oxidase activity in
prelaminar vs postlaminar regions in patient A was significant
(P<.001,
t299 = 26.93). For patient
B, the comparison was also significant (P<.001,
t199 = 29.36; Figure
3).
|
|
|
|
Figure 3. Relative cytochrome-c
oxidase (COX) activity across regions of the optic nerve head in patients A and B.
|
|
|
The pig optic nerve has a similar arrangement to the human,
although the laminar structure is placed in a more anterior position.
In the sections studied, myelination corresponded closely to
the posterior lamina. As in the human optic nerve,
cytochrome-c oxidase activity was inversely related
to myelination.
The rabbit optic nerve has a different structure. Sudan black B fat
staining confirmed that the optic nerve head in these animals is
myelinated throughout. Immunocytochemistry using laminin antibodies
also confirmed that there is no organized laminar structure.
When compared with pig and human tissue, cytochrome-c
oxidase activity in the rabbit was low and uniform throughout the optic
nerve head. Serial sections of
the retina at the myelination interface show low
cytochrome-c oxidase activity in the myelinated nerve fibers,
similar to that seen in the optic nerve head, and higher
cytochrome-c oxidase activity in the unmyelinated nerve
fibers. These features are demonstrated in Figure
4.
|
|
|
|
Figure 4.
Rabbit retina and optic nerve. A, A composite picture of the rabbit
retina: cytochrome-c oxidase histochemistry. Arrows indicate
the nerve fiber layer; 1, unmyelinated region; 2, transition zone where
myelination begins; and 3, fully myelinated region.
Cytochrome-c oxidase activity in the retinal nerve fiber layer
decreases as soon as myelination begins. B, Corresponding composite
picture stained with Sudan black B fat to show myelination. Areas 1
through 3 are the same as in part A. C, Rabbit optic nerve stained with
Sudan black B fat, demonstrating that the optic nerve head is
myelinated throughout. D, Rabbit optic nerve labeled by
cytochrome-c oxidase histochemistry, demonstrating a uniformly low enzyme activity. Original magnification x40 for all illustrations.
|
|
|
Immunocytochemical labeling with antibody SMI 31 confirmed that
sections of pituitary stalk contained the neurohypophysial tract. Sudan
black B fat staining also demonstrated that these nerve fibers were
unmyelinated. There was a stark contrast between the low
cytochrome-c oxidase activity of surrounding
pituitary tissue and the reaction seen in the unmyelinated
neurohypophysial fibers, which was comparable to that of an
unmyelinated human optic nerve head of a similar age despite a
considerably longer postmortem delay. These features are demonstrated
in Figure 5.
|
|
|
|
Figure 5.
Human unmyelinated neurohypophysial tract with surrounding pituitary
tissue. A, Sudan black B fat staining demonstrates unmyelinated tract
fibers.
B, Cytochrome-c oxidase histochemistry shows
relatively higher activity within the unmyelinated fibers compared with
the surrounding pituitary tissue. Original magnification x40 for both
illustrations.
|
|
|
COMMENT
The concept of constriction at the lamina cribrosa of the optic nerve
originates from the work of Weiss and Hiscoe9 on large
myelinated fibers, published in 1948. They simulated compression with
arterial sleeves and observed a buildup of axoplasmic material proximal
to the strictures.9 Similarities were drawn between this
and normal optic nerve despite obvious differences between these 2
tissues. Many researchers2-3,10 followed, observing
increased accumulation of mitochondria with increased intraocular
pressure. Minckler et al4 found increased numbers of
mitochondria at the level of the lamina in the rhesus monkey, but
failed to show any reduction in axonal diameter during passage through
the lamina. In addition,
bearing in mind that mitochondria are fluid
structures able to assume different shapes to conform to their
environment,11 the study demonstrated no change in the size
of mitochondria to support a constriction theory. A more recent study
of active transport components in the guinea pig optic nerve by Ou et
al12 reported a reduction in active transport components
responsible for mitochondrial carriage at the level of the lamina and a
corresponding increase in mitochondrial numbers. This and other
studies13 have developed our understanding of mitochondrial
movement, indicating a much more active ordered mechanism than
previously thought.
Our study of normal human optic nerve tissue demonstrates a distinct
distribution of mitochondrial enzyme activity. Unmyelinated prelaminar
and laminar regions display high mitochondrial enzyme activity when
compared with postlaminar myelinated regions.
We found that histochemical and immunocytochemical labeling is useful
and can be used to make comparisons between differing regions of
individual optic nerves.
We sought to look closely at the relationship of mitochondrial activity
to the laminar structure and myelination. This is a difficult task in
the human optic nerve because the posterior border of the lamina is
usually closely related to the onset of myelination.
Furthermore, it is difficult to define the posterior limit of the
laminar structure on longitudinal section. Despite these limitations,
there are regional differences in individuals and the mitochondrial
enzyme activity more closely correlates with myelination than with
laminar structure. While most mammals have a similar optic nerve
arrangement, the rabbit provides an excellent opportunity to test our
hypothesis.
Demonstration of a transition in mitochondrial enzyme activity from
high to low in the nerve fiber layer at the point of myelination on the
retina supports our hypothesis.
A study of pituitary stalk unmyelinated nerve fibers showing similar
mitochondrial enzyme activity to the unmyelinated region of the human
optic nerve provides further evidence to suggest that levels seen in
the optic nerve are not artificially high due to primary axoplasmic
stasis but rather reflect a dynamic functional requirement of this part
of the nerve.
The main function of mitochondria is the production of adenosine
triphosphate energy, which is essential for any cell's survival.
Individual cells have differing metabolic requirements, and this is
also true at an intracellular level. Previous studies6, 14
have shown that, in the retina, differing cell layers have varying
cytochrome-c oxidase activities. Furthermore, within the
photoreceptor cells, the outer segments show a high degree of
cytochrome-c oxidase activity when compared with inner
segments because they require an enormous amount of energy for
maintenance of their membrane potential. This region of the cell is
packed with mitochondria.14 We suggest that the retinal
ganglion cell and its axon also display differing requirements.
Myelinated nerve fibers conduct by saltatory conduction, while
unmyelinated fibers require more energy to repolarize the plasma
membrane. Therefore, the unmyelinated prelaminar and laminar
regions require more mitochondrial enzyme activity. While
this study is based on histochemical demonstration of mitochondrial
activity, other structural investigations support this idea. Electron
microscopic studies conducted by Hollander et al1
demonstrated more mitochondria on both sides of the human lamina
cribrosa in unmyelinated fibers in the human optic nerve and no
accumulations in myelinated fibers. In rabbits, in which most fibers
were myelinated, accumulations of mitochondria were not seen.
While these findings were interpreted as evidence of antegrade and
orthograde flow restriction in unmyelinated fibers by the lamina
cribrosa, this study would also support our hypothesis. Our
observations differ in that we did not find a significant gradient of
cytochrome-c oxidase activity relating to laminar position
along the length of the unmyelinated fibers. Other
work15-16 has shown that, in myelinated fibers,
mitochondria collect in the nodes of Ranvier, where the membrane
potential undergoes flux.
Hepplemann et al17 studied the peripheral afferent nerve
fiber in the cat, commenting that the unmyelinated region of the fiber
contained more mitochondria than the myelinated segment. A
study18 of mutant rats with
unmyelinated optic nerves reported an increase in
the numbers of mitochondria compared with controls. Finally, a
study19 of cats in which optic nerve demyelination was
induced while preserving axoplasmic transport showed an initial
increase in mitochondrial numbers in the demyelinated segment, which
then decreased to normal levels during remyelination.
Our work and that of others cited suggest that mitochondrial enzyme
activity is tailored to the needs of specific regions and that this
relates not only to different tissues but also to individual cells. It
is possible that, in disease processes, mitochondrial movement is
altered in an attempt to compensate and maintain function.
Given that the unmyelinated optic nerve has a high relative demand for
mitochondrial enzyme activity, this region may also be extremely
sensitive to mitochondrial deficits. This might explain why optic
neuropathies occur in those with mitochondrial inherited diseases.
Leber hereditary optic neuropathy specifically targets the optic nerve,
but other mitochondrial inherited diseases, including myoclonic
epilepsy and ragged red fibers, chronic progressive external
ophthalmoplegia, Leigh syndrome, and mitochondrial encephalopathy,
lactic acidosis, and strokelike episodes syndrome are also associated
with optic nerve malfunction.20 While these mitochondrial
inherited diseases are relatively rare, our hypothesis also challenges
our approach to other more common optic neuropathies, such as glaucoma.
More work is needed to advance our understanding of the dynamics of
mitochondrial distribution, movement, and function in disease
processes.
AUTHOR INFORMATION
Submitted for publication August 10, 2001; final revision received
January 23, 2002; accepted February 5, 2002.
This study was supported by a grant from the International Glaucoma
Association, London, England.
We thank the Newcastle Medical Research Council brain bank, Newcastle
upon Tyne, England, for donating the sample of pituitary stalk tissue;
and Jan-Willem Taanman, PhD, for supplying the mouse monoclonal
antibody to cytochrome-c oxidase subunit II.
Reprints not available from the authors.
Corresponding author: Elizabeth A. Bristow, FRCOphth, Department
of Ophthalmology, Royal Victoria Infirmary, Queen Victoria Road,
Newcastle upon Tyne NE1 4LP, England (e-mail: lizbristow{at}hotmail.com).
From the Department of Ophthalmology, Royal Victoria
Infirmary (Drs Bristow, Griffiths, and Andrews), and the Department of
Neurosciences, University of Newcastle (Drs Johnson and Turnbull),
Newcastle upon Tyne, England.
REFERENCES
| |
1. Hollander H, Makarov F, Stefant FH, et al. Evidence of constriction of
the optic nerve axons at the lamina cribrosa in the normotensive eye in
humans and other mammals. Ophthalmic Res. 1995;27:296-309.
ISI
| PUBMED
2. Quigley HA, Addicks EM. Chronic experimental glaucoma in primates, II:
effect of extended intraocular pressure elevation on optic nerve head
and axonal transport. Invest Ophthalmol Vis Sci. 1980;19:137-152.
FREE FULL TEXT
3. Radius RL, Douglas MD, Anderson R. Rapid axonal transport in primate
optic nerve: distribution of pressure-induced interruption. Arch
Ophthalmol. 1981;99:650-659.
FREE FULL TEXT
4. Minckler DS, McLean IW, Tso MOM. Distribution of axonal and glial
elements in the rhesus optic nerve head studied by electron microscopy. Am J Ophthalmol. 1976;82:179-187.
ISI
| PUBMED
5. Davis FA. The anatomy and histology of the eye and orbit of the rabbit. Trans Am Ophthalmol Soc. 1929;27:401-441.
6. Andrews R, Griffiths PG, Johnson MA, Turnbull DM. Histochemical
localisation of mitochondrial enzyme activity in human optic nerve and
retina. Br J Ophthalmol. 1999;83:231-235.
FREE FULL TEXT
7. Taanman JW, Burton MD, Marusich MF, Kennaway NG, Capaldi RA. Subunit specific monoclonal antibodies show different steady-state levels of
various cytochrome-c oxidase subunits in chronic
progressive external ophthalmoplegia. Biochim Biophys Acta. 1996;1315:199-207.
PUBMED
8. Lessell S, Horovitz B. Histochemical study of enzymes of optic nerve of
monkey and rat. Am J Ophthalmol. 1972;74:118-126.
ISI
| PUBMED
9. Weiss P, Hiscoe HB. Experiments on the mechanisms of nerve growth. J Exp Zool. 1948;107:315-395.
FULL TEXT
|
ISI
| PUBMED
10. Quigley HA, Addicks EM, Green WR, et al. Optic nerve damage in human
glaucoma. Arch Ophthalmol. 1981;99:635-649.
FREE FULL TEXT
11. Bradford HF. Chemical Neurobiology: An Introduction to
Neurochemistry. New York, NY: WH Freeman & Co; 1986:10.
12. Ou B, Ohno S, Tsukahara S. Ultrastructural changes and
immunocytochemical localization of microtubule-associated protein 1 in
guinea pig optic nerves after acute increase in intraocular pressure. Invest Ophthalmol Vis Sci. 1998;39:963-971.
FREE FULL TEXT
13. Sloan KE, Stevenson JA. Differential distribution of phosphorylated and
non-phosphorylated neurofilaments within the retina and optic nerve of
hamsters. Brain Res. 1987;437:365-368.
FULL TEXT
|
ISI
| PUBMED
14. Kageyama GH, Wong-Riley M. The histochemical localization of cytochrome
oxidase in the retina and lateral geniculate nucleus of the ferret,
cat, and monkey, with particular reference to retinal mosaics and
on/off-center visual channels. J Neurosci. 1984;4:2445-2459.
ABSTRACT
15. Berthold CH, Fabricius C, Rydmark M, et al. Axoplasmic organelles at
the nodes of Ranvier, I: occurrence and distribution in large
myelinated spinal root axons of the adult cat. J Neurocytol. 1993;22:925-940.
FULL TEXT
|
ISI
| PUBMED
16. Waxman SG, Ritchie JM. Molecular dissection of the myelinated axon. Ann Neurol. 1993;33:121-136.
FULL TEXT
|
ISI
| PUBMED
17. Hepplemann B, Messlinger K, Neiss WF, et al. Mitochondria in fine
afferent nerve fibres of the knee joint in the cat: a quantitative
electron-microscopical examination. Cell Tissue Res. 1994;275:493-501.
FULL TEXT
|
ISI
| PUBMED
18. Dentinger MP, Barron KD, Csiza CK. Glial and axonal development in
optic nerve of myelin deficient rat mutant. Brain Res. 1985;344:255-266.
FULL TEXT
|
ISI
| PUBMED
19. Mutsaers SE, Carroll WM. Focal accumulation of intra-axonal mitochondria in demyelination of the cat optic nerve. Acta Neuropathol (Berl). 1998;96:139-143.
FULL TEXT
| PUBMED
20. Newman NJ. Mitochondrial disease and the eye. Ophthalmol Clin
North Am. 1992;5:405-424.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Mitochondrial changes within axons in multiple sclerosis
Mahad et al.
Brain 2009;132:1161-1174.
ABSTRACT
| FULL TEXT
Inherited mitochondrial optic neuropathies
Yu-Wai-Man et al.
J. Med. Genet. 2009;46:145-158.
ABSTRACT
| FULL TEXT
Intraocular Pressure Elevation Induces Mitochondrial Fission and Triggers OPA1 Release in Glaucomatous Optic Nerve
Ju et al.
IOVS 2008;49:4903-4911.
ABSTRACT
| FULL TEXT
Mitochondrial Membrane Potential in Axons Increases with Local Nerve Growth Factor or Semaphorin Signaling
Verburg and Hollenbeck
J. Neurosci. 2008;28:8306-8315.
ABSTRACT
| FULL TEXT
Elevated Hydrostatic Pressure Triggers Mitochondrial Fission and Decreases Cellular ATP in Differentiated RGC-5 Cells
Ju et al.
IOVS 2007;48:2145-2151.
ABSTRACT
| FULL TEXT
Cerebrospinal fluid dynamics between the intracranial and the subarachnoid space of the optic nerve. Is it always bidirectional?
Killer et al.
Brain 2007;130:514-520.
ABSTRACT
| FULL TEXT
Linezolid-induced optic neuropathy: a mitochondrial disorder?
Javaheri et al.
Br. J. Ophthalmol. 2007;91:111-115.
ABSTRACT
| FULL TEXT
Diabetic Retinopathy: Seeing Beyond Glucose-Induced Microvascular Disease
Antonetti et al.
Diabetes 2006;55:2401-2411.
ABSTRACT
| FULL TEXT
A hypothesis to suggest that light is a risk factor in glaucoma and the mitochondrial optic neuropathies
Osborne et al.
Br. J. Ophthalmol. 2006;90:237-241.
ABSTRACT
| FULL TEXT
The axonal transport of mitochondria
Hollenbeck and Saxton
J. Cell Sci. 2005;118:5411-5419.
ABSTRACT
| FULL TEXT
Expression of the Opa1 Mitochondrial Protein in Retinal Ganglion Cells: Its Downregulation Causes Aggregation of the Mitochondrial Network
Kamei et al.
IOVS 2005;46:4288-4294.
ABSTRACT
| FULL TEXT
Mitochondrial disorders
Zeviani and Di Donato
Brain 2004;127:2153-2172.
ABSTRACT
| FULL TEXT
Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia
Edgar et al.
JCB 2004;166:121-131.
ABSTRACT
| FULL TEXT
Developmental Expression Profile of the Optic Atrophy Gene Product: OPA1 Is Not Localized Exclusively in the Mammalian Retinal Ganglion Cell Layer
Aijaz et al.
IOVS 2004;45:1667-1673.
ABSTRACT
| FULL TEXT
The distributions of mitochondria and sodium channels reflect the specific energy requirements and conduction properties of the human optic nerve head
Barron et al.
Br. J. Ophthalmol. 2004;88:286-290.
ABSTRACT
| FULL TEXT
Response of Mitochondrial Traffic to Axon Determination and Differential Branch Growth
Ruthel and Hollenbeck
J. Neurosci. 2003;23:8618-8624.
ABSTRACT
| FULL TEXT
Mitochondrial Function and Dysfunction Within the Optic Nerve
Sadun and Carelli
Arch Ophthalmol 2003;121:1342-1343.
FULL TEXT
Optic Neuropathy Induced by Reductions in Mitochondrial Superoxide Dismutase
Qi et al.
IOVS 2003;44:1088-1096.
ABSTRACT
| FULL TEXT
Varicosities of Intraretinal Ganglion Cell Axons in Human and Nonhuman Primates
Wang et al.
IOVS 2003;44:2-9.
ABSTRACT
| FULL TEXT
|
