兔视神经间接损伤病理学观察

目的　观察视神经间接损伤后病理学过程。方法　选用７２ 只兔（１４４ 只眼）制作视神经间接损伤动物模型,随机分为单纯致伤组和激素治疗组。动态行光镜和电镜观察,采用计算机行轴突计数。结果　视神经间接损伤后主要表现为水肿、髓鞘脱失、髓鞘再生和轴突的改变。激素治疗组的水肿较轻（Ｐ＜０－０１）,有髓纤维计数较多。结论　视神经发生间接损伤后主要改变是神经的水肿、脱髓鞘和轴突的变化。激素有一定的治疗作用。     

Optic nerve degeneration in a murine model of juvenile ceroid lipofuscinosis

PURPOSE: To investigate optic nerve degeneration associated with CLN3 deficiency in a murine model of juvenile neuronal ceroid lipofuscinosis (Batten disease). METHODS: Using light and electron microscopy, the density and diameter of axons and the thickness of myelin in optic nerve were compared between age-matched cln3 knock-out (cln3-/-) and wild-type (129ev/TAC) mice. Western blot analysis was used to assay expression of Cln3 in mouse and primate retina and optic nerve. RESULTS: Morphologically identified mast cells were present in the meningeal sheaths surrounding the cln3-/- nerve and in the nerve itself. The cln3-/- optic nerve exhibited an overall loss of uniformity and integrity. Axon density in cln3-/- optic nerve was only 64% of that in wild-type optic nerve (P < 0.01). Accounting for differences in axon density, the diameter of axons in cln3-/- optic nerve was 1.2 times greater than in wild-type optic nerve (P < 0.01). Electron micrographs revealed large spaces between axons and 32% thinner myelin surrounding axons in cln3-/- mice than in wild type (P < 0.01). Western blot analysis demonstrated that Cln3 was expressed in retinas and optic nerves of mouse and primate. CONCLUSIONS: The presence of apparent mast cells in cln3-/- optic nerve suggests compromise of the blood-brain barrier. The absence of Cln3 causes loss of axons, axonal hypertrophy, and a reduction in myelination of retinal ganglion cells. Furthermore, expression of CLN3 in mouse and primate optic nerve links degeneration to loss of Cln3.     

Optic nerve transection in monkeys may result in secondary degeneration of retinal ganglion cells

PURPOSE: Interest in neuroprotection for optic neuropathies is, in part, based on the assumption that retinal ganglion cells (RGCs) die, not only as a result of direct (primary) injury, but also indirectly as a result of negative effects from neighboring dying RGCs (secondary degeneration). This experiment was designed to test whether secondary RGC degeneration occurs after orbital optic nerve injury in monkeys. METHODS: The superior one third of the orbital optic nerve on one side was transected in eight cynomolgus monkeys (Macaca fascicularis). Twelve weeks after the partial transection, the number of RGC bodies in the superior and inferior halves of the retina of the experimental and control eyes and the number and diameter of axons in the optic nerve were compared by detailed histomorphometry. Vitreous was obtained for amino acid analysis. A sham operation was performed in three additional monkeys. RESULTS: Transection caused loss of 55% +/- 13% of RGC bodies in the superior retina of experimental compared with fellow control eyes (mean +/- SD, t-test, P < 0.00,001, n = 7). Inferior RGCs, not directly injured by transection, decreased by 22% +/- 10% (P = 0.002). The loss of superior optic nerve axons was 83% +/- 12% (mean +/- SD, t-test, P = 0.0008, n = 5) whereas, the inferior loss was 34% +/- 20% (P = 0.02, n = 5). Intravitreal levels of glutamate and other amino acids in eyes with transected nerves were not different from levels in control eyes 12 weeks after injury. Fundus examination, fluorescein angiography, and histologic evaluation confirmed that there was no vascular compromise to retinal tissues by the transection procedure. CONCLUSIONS: This experiment suggests that primary RGC death due to optic nerve injury is associated with secondary death of surrounding RGCs that are not directly injured.     

TNF-alpha-induced optic nerve degeneration and nuclear factor-kappaB p65

PURPOSE: To characterize a model of optic nerve axonal degeneration induced by tumor necrosis factor (TNF)-alpha and to determine the role of nuclear factor (NF)-kappaB p65 in axonal degeneration. METHODS: Groups of rats were euthanatized at 1 day, 1 or 2 weeks, or 1 or 2 months after intravitreal injection of TNF-alpha. Morphometric analyses of neurofilament- or Thy-1-positive cells, retinal ganglion cells (flat preparations stained with cresyl violet or retrograde labeling with a neurotracer), the number of axons, immunostaining for myelin basic protein, and TUNEL assays were performed. Levels of NF-kappaB p65 protein in retina and optic nerve were determined by Western blot analysis and immunohistochemistry. The effects of antisense oligodeoxynucleotide (AS ODN) against NF-kappaB p65 and helenalin, an inhibitor of NF-kappaB p65 activation, on TNF-alpha-induced optic nerve degeneration were determined by counting the number of axons. RESULTS: Intravitreal injections of TNF-alpha induced obvious axonal loss and extensive degeneration of the axons from 2 weeks to 2 months after injection, whereas significant retinal ganglion cell loss was noted only at 2 months after injection. NF-kappaB p65 was increased in the optic nerve but not in the retina and was found to colocalize with ED-1 and Iba1, markers of microglia. Inhibition of NF-kappaB p65 with AS ODN or helenalin significantly ameliorated the effects of TNF-alpha-mediated axonal loss. CONCLUSIONS: TNF-alpha causes axonal degeneration with probable delayed loss of retinal ganglion cell bodies. NF-kappaB p65 may play a pivotal role in axonal degeneration, with the possible involvement of microglial cells.     

Mechanism of retinal ganglion cells death in secondary degeneration of the optic nerve

In central nervous system injury, the secondary degeneration process is known to play a major role in determining the final extent of impairment. Here, we investigated the mechanism of retinal ganglion cell (RGC) death in secondary degeneration of the optic nerve using a unique model that allows morphological separation between primary and secondary degeneration. A partial transection model was applied unilaterally in 110 Wistar rat eyes. The rate of apoptosis was evaluated in primary and secondary degeneration over a period of 6 months using the Hoechst staining technique. The involvement of caspase 3 and members of the Bcl-2 family (Bax, Bad, Bcl-2 and Bcl-xl) was evaluated at multiple time points for 6 months after the injury by immunohistochemistry and RT-PCR. We found that in secondary degeneration of the optic nerve, RGCs died by apoptosis from day 3-6 months following the injury, peaking at 3 months (16.3% ± 2.5% apoptotic cells, p < 0.01). Both primary and secondary degeneration of the optic nerve resulted in caspase 3 activation, which was longer and more intense in the former. Similarly, both primary and secondary degeneration led to significant (p < 0.05) downregulation of the pro-survival genes Bcl-2 and Bcl-x-L and up-regulation of the pro-apoptotic genes Bax and Bad (p < 0.05), with a suggested delay in secondary degeneration. Thus, secondary degeneration of the optic nerve leads to RGC apoptosis over long periods in a similar mechanism as in primary degeneration.     

Optic nerve alterations in P27(Kip1) knockout mice

PURPOSE: To study the morphologic characteristics of the optic nerve (ON) by using an experimental model of knockout mice for the expression of the P27(Kip1) gene, mainly involved in cell cycle arrest, apoptosis control, and retinoblastoma protein phosphorylation. METHODS: Eyeballs with the retrobulbar ON attached were obtained from 26-week-old mice. By using morphologic and morphometric techniques, light and electron transmission microscopy, the ON characteristics were determined in two groups of mice: 1) wild type mice as the control group (n=15), 2) homozygous knockout mice (-/-) for the P27(Kip1) gene as the knockout group (n=15). Glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) were studied using Western blot and immunoblotting approaches. RESULTS: The ON cross-sectional area was significantly larger in the P27(Kip1) knockout mice group than in the control group (p<0.001). The axon sizes in knockout animals were much larger than in wild-type mice (p<0.001). Higher number of axons forming the ON, intra-axonal degeneration, myelin sheath, and axoplasm density alterations were found in P27(Kip1) knockout mice when compared with control group (p<0.001). Analysis of lysates of optic nerves by Western blot showed less expression of myelin basic protein and GFAP in P27(Kip1) knockout mice as compared to wild type mice (p<0.005, p<0.01, respectively). CONCLUSIONS: The morphologic and morphometric results suggest that homozygous P27(Kip1) knock-out mice had hypertrophic, hyperplastic, and dystrophic ON.     

A model to study differences between primary and secondary degeneration of retinal ganglion cells in rats by partial optic nerve transection

PURPOSE: To use a rat model of optic nerve injury to differentiate primary and secondary retinal ganglion cell (RGC) injury. METHODS: Under general anesthesia, a modified diamond knife was used to transect the superior one third of the orbital optic nerve in albino Wistar rats. The number of surviving RGC was quantified by counting both the number of cells retrogradely filled with fluorescent gold dye injected into the superior colliculus 1 week before nerve injury and the number of axons in optic nerve cross sections. RGCs were counted in 56 rats, with 24 regions examined in each retinal wholemount. Rats were studied at 4 days, 8 days, 4 weeks, and 9 weeks after transection. The interocular difference in RGCs was also compared in five control rats that underwent no surgery and in five rats who underwent a unilateral sham operation. It was confirmed histologically that only the upper optic nerve had been directly injured. RESULTS: At 4 and 8 days after injury, superior RGCs showed a mean difference from their fellow eyes of -30.3% and -62.8%, respectively (P = 0.02 and 0.001, t-test, n = 8 rats/group), whereas sham-operation eyes had no significant loss (mean difference between eyes = 1.7%, P = 0.74, t-test). At 8 days, inferior RGCs were unchanged from control, fellow eyes (mean interocular difference = -4.8%, P = 0.16, t-test). Nine weeks after transection, inferior RGC had 34.5% fewer RGCs than their fellow eyes, compared with 41.2% fewer RGCs in the superior zones of the injured eyes compared with fellow eyes. Detailed, serial section studies of the topography of RGC axons in the optic nerve showed an orderly arrangement of fibers that were segregated in relation to the position of their cell bodies in the retina. CONCLUSIONS: A model of partial optic nerve transection in rats showed rapid loss of directly injured RGCs in the superior retina and delayed, but significant secondary loss of RGCs in the inferior retina, whose axons were not severed. The findings confirm similar results in monkey eyes and provide a rodent model in which pharmacologic interventions against secondary degeneration can be tested.     

Ciliary neuromuscular morphology in cynomolgus monkeys after ciliary ganglionectomy

Cynomolgus monkeys underwent unilateral ciliary ganglionectomy (CG) and/or posterior ciliary neurectomy (PCN). The ciliary muscle was functionally denervated, as evidenced by loss of choline acetyltransferase activity, loss of the accommodative response to topical eserine and electrical stimulation of the Edinger-Westphal nucleus, and supersensitivity of the accommodative response to pilocarpine [5, 6, 7]. Light and electron microscopy carried out 3–28 days after CG/PCN revealed degeneration of myelinated and unmyelinated nerve fibers as evidenced by axonal swelling and shrinkage, mitochondrial degeneration, axoplasmic condensation and vacuolization, and activated, phagocytosing Schwann cells. By 1–3 months after CG/PCN, few non-myelinated axons remained between the muscle bundles, larger nerve bundles were disordered and deteriorated, and Schwann cells filled with lipid and cellular debris were prominent. Beyond 6 months (6–37 months), most eyes were reinnervated by functional criteria. Concurrently, the ciliary neuromuscular morphology appeared virtually normal, exhibiting many non-myelinated axons containing numerous agranular synaptic vesicles and large mitochondria; however, remnants of degenerated axons were still present. In two eyes remaining functionally denervated, many of the unmyelinated axons between the ciliary muscle bundles were swollen or empty, with small, degenerated mitochondria and only rare synaptic vesicles, and were often ensheathed by thickened, condensed Schwann-cell cytoplasm. The muscle fibers were atrophic and separated from each other as well as from the ensheathed nerve fibers. Thus, following CG/PCN, the morphologic and functional evidence of parasympathetic denervation and reinnervation of the ciliary muscle is pathophysiologically and temporally consistent.     

Optic nerve changes in zinc-deficient rats

In this study the optic nerve changes in zinc (Zn)-deficient rats are examined. Zinc is one of the essential trace elements and is known to be related to optic nerve diseases such as ethambutol neuropathy. However, the effect of Zn on the optic nerve has not been studied experimentally in animals. We used 3 week old weanling male Wistar Kyoto rats weighing 40-50 g. Rats were fed a Zn-deficient diet containing 0.007 mg of Zn per 100 g, all other nutrients and distilled and deionized water. The same water supplemented with 3 mg Zn per 100 g was given to the control group. After 4 or 7 weeks on a Zn-deficient diet, the optic nerve was examined with an electron microscope. A recovery group was fed a Zn-containing diet for 5 weeks after 7 weeks on the Zn-deficient diet. The serum Zn levels of the deficient group were significantly decreased at both 4 and 7 weeks. Most of the Zn-deficient rats showed hair loss around the eyes and on the extremities. Ultrastructural findings were as follows. The number of myelinated axons of Zn-deficient rats at 4 and 7 weeks were significantly decreased and the myelin sheaths were significantly thinner in the Zn-deficient groups and in the recovery group. Unmyelinated axons were more numerous than in the control rats. Destruction of myelin and proliferation of glial cells were found in the optic nerves of Zn-deficient rats. This study suggests that the optic nerve needs Zn for the maintenance of its cell structure and even if Zn is supplied to the Zn-deficient rats, destruction of the myelin structure may continue. Zn-deficiency induce a decrease of myelinated nerve fibers, and it is thought that optic neuropathy in patients treated with some drugs such as ethambutol may be a secondary change due to Zn-deficiency following drug administration.     

Vulnerability of dopaminergic amacrine cells and optic nerve myelination to prenatal endotoxin exposure

PURPOSE: Intrauterine infection has been linked to preterm delivery and neurologic injury. The purpose of this study was to investigate the effects of fetal inflammation induced by exposure to endotoxin on the structure and neurochemistry of the retina and optic nerve. METHODS: The bacterial endotoxin, lipopolysaccharide (LPS), was administered to fetal sheep at approximately 0.65 of the approximately 147-day gestation period via repeated bolus doses (1 microg/kg per day) over 5 days, with fetal retinas and optic nerves assessed 10 days after the first LPS exposure. RESULTS: In the retina, the total number of tyrosine hydroxylase immunoreactive (TH-IR), dopaminergic amacrine cells was reduced (P < 0.05) in LPS-exposed compared with control fetuses. There was no difference in the number of ChAT-, substance P-, or NADPH-d-positive amacrine cells. The total number of myelinated axons in the optic nerve was not different (P > 0.05) between groups; however, the myelin sheath was thinner (P < 0.05) in LPS-exposed fetuses. CONCLUSIONS: Prenatal exposure to repeated doses of endotoxin results in alterations to the retina and optic nerve with specific effects on dopaminergic neurons and myelination, respectively. These findings could have implications for visual function.     

Role of glia in optic nerve

Glial cells are critically important for maintenance of neuronal activity in the central nervous system (CNS), including the optic nerve (ON). However, the ON has several unique characteristics, such as an extremely high myelination level of retinal ganglion cell (RGC) axons throughout the length of the nerve (with virtually all fibers myelinated by 7 months of age in humans), lack of synapses and very narrow geometry. Moreover, the optic nerve head (ONH) – a region where the RGC axons exit the eye – represents an interesting area that is morphologically distinct in different species. In many cases of multiple sclerosis (demyelinating disease of the CNS) vision problems are the first manifestation of the disease, suggesting that RGCs and/or glia in the ON are more sensitive to pathological conditions than cells in other parts of the CNS. Here, we summarize current knowledge on glial organization and function in the ON, focusing on glial support of RGCs. We cover both well-established concepts on the important role of glial cells in ON health and new findings, including novel insights into mechanisms of remyelination, microglia/NG2 cell-cell interaction, astrocyte reactivity and the regulation of reactive astrogliosis by mitochondrial fragmentation in microglia.     

Human intraretinal myelination: Axon diameters and axon/myelin thickness ratios

Purpose:

Human intraretinal myelination of ganglion cell axons occurs in about 1% of the population. We examined myelin thickness and axon diameter in human retinal specimens containing myelinated retinal ganglion cell axons.

Materials and Methods:

Two eyes containing myelinated patches were prepared for electron microscopy. Two areas were examined in one retina and five in the second retina. Measurements were compared to normal retinal and optic nerve samples and the rabbit retina, which normally contains myelinated axons. Measurements were made using a graphics tablet.

Results:

Mean axon diameter of myelinated axons at all locations were significantly larger than unmyelinated axons (P ≤ 0.01). Myelinated axons within the patches were significantly larger than axons within the optic nerve (P < 0.01). The relationship between axon diameter/fiber diameter (the G-ratio) seen in the retinal sites differed from that in the nerve. G-ratios were higher and myelin thickness was positively correlated to axon diameter (P < 0.01) in the retina but negatively correlated to axon diameter in the nerve (P < 0.001).

Conclusion:

Intraretinally myelinated axons are larger than non-myelinated axons from the same population and suggests that glial cells can induce diameter changes in retinal axons that are not normally myelinated. This effect is more dramatic on intraretinal axons compared with the normal transition zone as axons enter the optic nerve and these changes are abnormal. Whether intraretinal myelin alters axonal conduction velocity or blocks axonal conduction remains to be clarified and these issues may have different clinical outcomes.     

米诺环素对急性视神经炎视神经轴突及Caspase-3表达的影响

目的:探讨米诺环素对急性视神经炎的影响,并与甲基强的松龙比较。方法:雌性Wistar大鼠22只随机分为正常组、EAE组、米诺环素组、甲基强的松龙组(MP组)。观察视神经病理改变,免疫组织化学法检测视网膜神经节细胞(retinal ganglion cells,RGCs)中Caspase-3蛋白表达。结果:EAE组视神经光镜下表现为神经纤维空泡样变性,轴突不规则肿胀,大量炎性细胞浸润。EAE组、米诺环素组、MP组与正常组视神经轴突占横切面积比例相比,差异均有显著统计学意义(P<0.01),米诺环素组、MP组与EAE组间的差异均有统计学意义(P<0.05)。正常大鼠视网膜几乎未见Caspase-3蛋白表达,EAE组、MP组与米诺环素组间的差异均有统计学意义(P<0.05),MP组与EAE组间的差异有统计学意义(P<0.05)。结论:甲基强的松龙可减轻脱髓鞘性视神经炎轴突损伤,但不能减少RGCs中Caspase-3的表达。米诺环素可下调Caspase-3在视网膜中表达,提示米诺环素可通过抑制RGCs中Caspase-3活性,介导对脱髓鞘性视神经炎RGCs的保护作用。     

Morphological Consequences of Myelination in the Human Retina

Intraretinal myelination of ganglion cell axons occurs in about 1% of humans and when observed ophthalmoscopically, appears as a white or opaque patch within the fiber layer. Previous studies of myelinated retinal tissue have largely been conducted at the light microscopic level. Three retinae with intraretinal myelination and one normal retina were obtained post-mortem and prepared for electron microscopy. The present study showed that myelinated patches in the human retina contained a mixture of unmyelinated and myelinated axons. Within this population of myelinated axons were structures which were abnormal and there were obvious signs of axonal and myelin sheath degeneration within the myelinated patches. Outside these myelin patches the retina appeared normal without signs of degeneration indicating that post-mortem degeneration prior to fixation could not account for all of the degenerative changes observed. The lack of significant numbers of macrophages and lymphocytes indicated that there was no concomitant inflammatory process within the myelin patches. The myelination present within these eyes appeared to be due to the anomalous location of oligodendrocytes. Both unmyelinated and myelinated axons had larger diameters than axons measured within normal areas of the retina or those within the optic nerve.     

Regeneration of the optic nerve of Xenopus laevis after argon laser injury]

Following mechanical lesion of the optic nerve (ON), lower vertebrates are capable of regeneration of the ON and regain visual function. We have studied, by light and electron microscopy, regeneration of the larval ON of Xenopus laevis after treatment with the argon laser. The laser energy is absorbed by the neurothelial pigment and provokes a burned crater and vesiculation in the interior of the ON. In contrast to the mechanically induced process, axons regenerate, after laser treatment, within the nerve and do not sprout into the neighboring tissue. The regenerating ON is not vascularized. Immediately after laser treatment, a loss of myelin, hypertrophy, phagocytic activity, and local rearrangement of glial cells are observed. After four weeks, myelination is still irregular. Glial cells have regained their normal aspect.     

Electrophysiological and histopathological study on visual toxicity of clioquinol

OBJECTIVE: To evaluate the effect of clioquinol on the optic nerve and retina of rhesus monkeys by ophthalmoscopy, electrophysiology and histopathology. METHODS: Clioquinol was given orally to 5 monkeys, gradually increasingly from 100 mg/kg/day up to 14 months(total dosage 227 g/kg). Ophthalmoscopy, erectroretinogram(ERG), visual evoked potential(VEP) and histopathological examination of enucleated eyeballs were done periodically up to 10 years. RESULTS: The margin of the optic disc was not clear at the early stage, but the colour became atrophic at the late stage. VEP maximum amplitude decreased quickly at the early stage and the amplitude of ERG a and b waves and oscillatory potential decreased gradually. 37 months after the discontinuation of administration of VEP, ERG amplitude increased gradually. Swelling of axons and disorganization of the myelin sheath were noticed 2.5 months after beginning treatment. Swelling of the peripapillary nerve fiber layer was seen 5.5 months after beginning treatment. Karyorrhexis was seen in the inner layer of the retina after 12.5 months. Axonal swelling disappeared and the myelin sheath became reorganized 9 months after the discontinuation of treatment. CONCLUSIONS: Clioquinol produced an early decrease of electrophysiological function, but recovery of function was seen after discontinuation of treatment. The degeneration of axons and myelin sheath continued during treatment, and interruption of the degeneration was seen after discontinuation of treatment.     

High intraocular pressure-induced ischemia and reperfusion injury in the optic nerve and retina in rats

• Purpose: The purpose of this paper is to describe the damage caused to the retina and the axons of the optic nerve by acute ischemia-reperfusion injury and the extent to which optic nerve damage correlates with the duration if ischemia due to high intraocular pressure (IOP). • Methods: Acute ischemia in the retina and optic disc was induced in albino rats by increasing the IOP to 110 mmHg for a period of 45–120 min. Thereafter, the eyes were reperfused at normal IOP after 7 days. The retina and optic nerve were examined by light and electron microscopy, and morphometrical counts of the optic nerve axons were performed. • Results: After 45 min of ischemia, electron microscopic examination revealed swelling of mitochondria and degeneration of neurotubules on axons in cross sections of the optic nerve. The axonal counts in eyes subjected to 45 min of ischemia were 29% lower than in control eyes. After 60 min of ischemia, there were distinct disruptions of mitochondria and degeneration of the axons. After 90 min of ischemia, numerous axons showed degeneration with disordered myelin sheaths. Neuronal cell death was seen in the retina, mainly in the ganglion cell layer. • Conclusion: Damage to the retinal ganglion cell layer and the optic nerve was evident after only 45 min of ischemia in normal eyes. This experiment suggests that seriously injured eyes must be protected from high IOP; if IOP elevation is required during vitrectomy, it is essential to reduce the duration of interruption of blood flow to a minimum.     

Expression of myocilin/TIGR in normal and glaucomatous primate optic nerves

Myocilin/TIGR was the first molecule discovered to be linked with primary open angle glaucoma (POAG), a blinding disease characterized by progressive loss of retinal ganglion cells. Mutations in myocilin/TIGR have been associated with age of disease onset and severity. The function of myocilin/TIGR and its role in glaucoma is unknown. Myocilin/TIGR has been studied in the trabecular meshwork to determine a role in regulation of intraocular pressure. The site of damage to the axons of the retinal ganglion cells is the optic nerve head (ONH). The myocilin/TIGR expression was examined in fetal through adult human optic nerve as well as in POAG. Myocilin/TIGR was expressed in the myelinated optic nerve of children and normal adults but not in the fetal optic nerve before myelination. Also examined was the expression in monkeys with experimental glaucoma. The results demonstrate that optic nerve head astrocytes constitutively express myocilin/TIGR in vivo in primates. Nevertheless, myocilin/TIGR is apparently reduced in glaucomatous ONH. The colocalization of myocilin/TIGR to the myelin suggests a role of myocilin/TIGR in the myelinated optic nerve.     

Anti-MOG (Myelin Oligodendrocyte Glycoprotein)–Positive Severe Optic Neuritis with Optic Disc Ischaemia and Macular Star

A 44-year-old man presented with severe right visual loss. The right fundus examination showed marked optic disc oedema associated with partial macular star. Serological blood tests for infectious agents were all negative. Serum aquaporin-4 antibody was negative but anti-MOG (myelin oligodendrocyte glycoprotein) was positive. Magnetic resonance revealed extensive lesion in right optic nerve. There was no visual improvement after intravenous therapy. Patient had no further attacks after follow-up. Optic disc oedema with macular star is found in several infectious and non-inflammatory disorders, but it has not been reported in optic neuritis (ON) associated with autoantibodies to myelin oligodendrocyte glycoprotein (anti-MOG).     

Axonal degeneration, regeneration and ganglion cell death in a rodent model of anterior ischemic optic neuropathy (rAION)

Using laser-induced photoactivation of intravenously administered rose Bengal in rats, we generated an ischemic infarction of the intrascleral portion of the optic nerve (ON) comparable to that which occurs in humans to investigate optic nerve axon degenerative events following optic nerve infarct and the potential for axon re-growth. Animals were euthanized at different times post infarct. Axon degeneration was evaluated with SMI312 immunolabeling, and GAP-43 immunostaining was used to identify axon regeneration. Terminal dUTP nick end labeling (TUNEL) was used to evaluate retinal ganglion cell (RGC) death. There was significant axon structural disruptinot ion at the anterior intrascleral portion of the ON by 3d post-infarct, extending to the posterior ON by 7d post-stroke. Destruction of normal axon structure and massive loss of axon fibers occurred by 2 weeks. GAP-43 immunoreactivity occurred in the anterior ON by 7d post-infarct, lasting 3-4 weeks, without extension past the primary ischemic lesion.TUNEL-positive cells in the RGC layer appeared by 7d post-insult. These results indicate that following induction of ischemic optic neuropathy, significant axon damage occurs by 3d post-infarct, with later neuronal death. Post-stroke adult rat retinal ganglion cells attempt to regenerate their axons, but this effort is restricted to the unmyelinated region of the anterior ON. These responses are important in understanding pathologic process that underlies human non-arteritic anterior ischemic optic neuropathy (NAION) and may guide both the appropriate treatment of NAION and the window of opportunity for such treatment.