Correlation of pseudoexfoliative material and optic nerve damage in pseudoexfoliation syndrome

PURPOSE: To determine whether the severity of glaucomatous damage in eyes with pseudoexfoliative (PEX) glaucoma is related to the amount of PEX material in the trabecular meshwork. METHODS: Trabecular meshwork and optic nerves from 19 eyes (11 donors) with PEX syndrome were studied. Eyes were chosen to represent all stages of severity of disease. Sections from each quadrant around the circumference of each eye were studied with light and transmission electron microscopy. Morphometric measurements were made of Schlemm's canal (SC) and of the components of the cribriform region and were statistically correlated with axonal counts of the optic nerves. Correlations between clinical and histologic data were determined. RESULTS: Pseudoexfoliative material was frequently found in isolated aggregates beneath the inner-wall endothelium of SC. The cribriform region was otherwise normal in structure; disorganization of this region was found only in focal regions of a few eyes. The amount of PEX material was correlated with the maximal intraocular pressure (IOP) and the IOP on treatment and was inversely correlated with the number of axons in the optic nerve. The number of axons was inversely correlated with the maximal IOP and the IOP on treatment, but not with duration of disease. CONCLUSIONS: The severity of glaucoma in PEX is related to the amount of PEX material present in the cribriform region. Elevation of IOP occurs before disorganization of the cribriform region and may be related to the location of the PEX material near the inner wall of SC. Comparison of clinical and histologic findings revealed that the results of visual field examinations fit more closely with the axonal counts than did the clinical assessment of the cup-to-disc ratio.     

Fluorescein angiography in chronic simple and low-tension glaucoma

Fluorescein angiograms were performed on a group of low-tension glaucoma and chronic simple glaucoma patients with similar extent of visual field loss, under standardised conditions, to see whether differences attributable to chronic intraocular pressure elevation could be detected. There was no evidence for difference in circulation times between these two groups. There was no evidence that hypoperfusion of the peripapillary choroid contributed to optic nerve hypoperfusion. Low-tension glaucoma patients demonstrated focal sector hypoperfusion of the optic nerve in every case, while the chronic simple glaucoma patients demonstrated a wide range of optic nerve fluorescence, suggesting both focal and diffuse optic nerve head hypoperfusion. It was concluded that, while focal hypoperfusion of the optic nerve may reflect susceptible vasculature at the nerve head with or without intraocular pressure elevation, diffuse hypoperfusion suggested that prolonged intraocular pressure elevation may simultaneously affect the whole of the optic nerve head. This could be a direct effect on blood vessels or a mechanical effect with secondary vascular changes.     

Normal and aberrant functions of integrins in the adult central nervous system

Eighteen normal human eye-bank eyes (age: 18-81 years), five fetal eyes (16-24 weeks), 11 primary open-angle glaucoma (POAG) eyes (age: 76-89 years), and two Schnabel's cavernous optic atrophy eyes were examined using a biotinylated-hyaluronan binding protein to study the changes in the distribution of hyaluronic acid (HA) in the fetal, adult and glaucomatous optic nerve head. The vitreous body served as a positive control. Sections treated with Streptomyces hyaluronidase were used to confirm specificity. Monoclonal antibodies to myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) were used as additional controls. In fetal optic nerve, HA was localized in blood vessels, peripapillary sclera and the pial septae in the retrolaminar nerve. No staining was associated with axons. Staining for MBP was negative. In adults, HA was found surrounding the myelin sheaths in the retrolaminar nerve; staining decreased with age. In contrast, HA staining in myelinated peripheral nerves (e.g. ciliaries) remained unchanged with age. HA also was localized to the adventitia of arteries and veins throughout the posterior segment. Compared to age-matched normal eyes, HA staining was virtually absent around myelin sheaths of the retrolaminar nerve in POAG eyes. Similar changes were not found in other HA positive structures. In Schnabel's cavernous optic atrophy. HA was present in increased amount in the atrophic area, but virtually absent in the remaining retrolaminar nerve. HA staining was invariably positive in vitreous, and Streptomyces hyaluronidase treated sections were negative. In adults, staining of MBP was associated with the myelin sheath in the retrolaminar nerve. In contrast to HA, staining of MBP was unchanged with age and in POAG. In Schnabel's atrophy, MBP staining disappeared only in the atrophic area. HA in the retrolaminar optic nerve appears to be associate with the space-filling matrix between myelin sheaths. HA is not present in the axon bundles prior to myelination of the optic nerve. HA in the retrolaminar optic nerve appears to decrease with age and is further reduced in POAG; however, corresponding changes are not found in MBP or in peripheral nerves. Perhaps, decreased amounts of HA is related to a higher susceptibility to elevated intraocular pressure or to optic nerve atrophy. In Schnabel's cavernous optic atrophy, HA is present in increased amount only in the atrophic area while MBP is markedly decreased, suggesting in situ production of HA in areas of optic nerve atrophy.     

Elevation of intraocular glutamate levels in rats with partial lesion of the optic nerve

BACKGROUND: Acute partial lesion of the rat optic nerve, although not a model for glaucoma, mimics some of the features of the disease. OBJECTIVE: To learn whether degeneration of rat optic nerve fibers and death of their retinal ganglion cells induced by an acute partial lesion are associated with elevated levels of glutamate, known to occur in the eyes of humans and monkeys with glaucoma. MATERIALS AND METHODS: Rat optic nerve was subjected to a partial crush injury. Aqueous humor samples were aspirated from the anterior and posterior aqueous chambers at specified times and their amino acid contents were determined by means of high-performance liquid chromatography. RESULTS: Three and 7 days after injury, intraocular glutamate and aspartate levels were found to be significantly higher than in normal or sham-operated-on eyes, and returned to normal by day 14. CONCLUSIONS: Degeneration of the optic nerve, induced by a mechanical injury of the axons, leads to intraocular elevation of glutamate and aspartate levels. These results illustrate that the model of the partial optic nerve lesion exhibits another feature typical of a long-term optic neuropathy, such as glaucoma.     

Laser scanning tomography of the optic nerve head in ocular hypertension and glaucoma

BACKGROUND: This study evaluated the ability of laser scanning tomography to distinguish between normal and glaucomatous optic nerve heads, and between glaucomatous subjects with and without field loss. METHODS: 57 subjects were classified into three diagnostic groups: subjects with elevated intraocular pressure, normal optic nerve heads, and normal visual fields (n = 10); subjects with glaucomatous optic neuropathy and normal visual fields (n = 30); and subjects with glaucomatous optic neuropathy and repeatable visual field abnormality (n = 17). Three 10 degrees image series were acquired on each subject using the Heidelberg retina tomograph (HRT). From the 14 HRT stereometric variables, three were selected a priori for evaluation: (1) volume above reference (neuroretinal rim volume), (2) third moment in contour (cup shape), and (3) height variation contour (variation in relative nerve fibre layer height at the disc margin). Data were analysed using analysis of covariance, with age as the covariate. RESULTS: Volume above reference, third moment in contour, and mean height contour were significantly different between each of the three diagnostic groups (p < 0.001). Height variation contour showed no significant difference among the three diagnostic groups (p = 0.906). CONCLUSIONS: The HRT variables measuring rim volume, cup shape, and mean nerve fibre layer height distinguished between (1) subjects with elevated intraocular pressures and normal nerve heads, and glaucomatous optic nerve heads, and (2) glaucomatous optic nerve heads with and without repeatable visual field abnormality. This study did not directly assess the ability of the HRT to identify patients at risk of developing glaucoma. It is hypothesised that the greatest potential benefit of laser scanning tomography will be in the documentation of change within an individual over time.     

Aging changes of the optic nerve head in relation to open angle glaucoma

AIMS: To determine the age related changes in optic nerve head structure in a group of normal subjects and assess the significance of any changes in relation to those found in open angle glaucoma. METHODS: A group of 88 white volunteers and friends and spouses of patients with a normal visual field and normal intraocular pressure was studied. Two different imaging and measurement devices were used (computer assisted planimetry and scanning laser ophthalmoscopy), and the results from each were compared. Measurements were made of the optic disc, optic cup, and neuroretinal rim areas, and the vertical optic disc diameter and cup/disc diameter ratio. RESULTS: Neuroretinal rim area declined at the rate of between 0.28% and 0.39% per year. Vertical optic cup diameter and optic cup area increased with age. The mean cup/disc diameter ratio increased by about 0.1 between the ages of 30 and 70 years. CONCLUSIONS: Age related changes are significant and measurable, and should be taken into account when assessing the glaucoma suspect, and when estimating the rate of progression of glaucomatous optic neuropathy in patients with established disease.     

Preoperative radiotherapy for prevention of heterotopic ossifications after hip endoprosthesis]

Glaucoma is a leading cause of blindness worldwide and the second leading cause of irreversible blindness in the United States. The most common form of glaucoma, primary open angle glaucoma, is characterized by a chronically elevated intraocular pressure in the absence of any demonstrable structural abnormalities in the eye. The pathologic hallmark of glaucomatous optic neuropathy is the selective death of retinal ganglion cells, generally attributed to an elevated intraocular pressure. However, the histopathology of glaucomatous injury is strikingly similar to the pattern seen with the administration of toxic levels of glutamate. We have found that glaucoma is associated with elevated levels of intraocular glutamate-to a level toxic to ganglion cells. We propose that an elevation of vitreal glutamate may be responsible, at least in part, for the loss of ganglion cells seen in open angle glaucoma.     

The Chiropractic Outcome Study: pain, functional ability and satisfaction with care

BACKGROUND: Elevation of intraocular pressure in the supine position has been previously described in literature. Aim of this study is to investigate the elevation of intraocular pressure in normal tension glaucoma and its effect on the morphology of the optic disc, visual field function and capillary blood flow of the retina and optic disc. PATIENTS AND METHODS: 56 eyes of 28 preperimetric and advanced normal tension glaucoma patients were prospectively evaluated. Ten eyes of ten normal patients served as a control group for the measurements of the intraocular pressure. In the course of a 24-h pressure profile applanation tonometry was performed in the morning in a supine and three and ten minutes later in a sitting position with Draeger's and Goldmann's tonometers. Arterial blood pressure was measured at the same time. The optic disc's morphology was evaluated by stereo photographs and Laser Scanning Tomography. As a sensory test computer perimetry was used. Capillary blood flow was measured at defined areas of the retina and optic disc. An intraocular pressure above 21 mm Hg in the supine position was used as a criterium to define two groups of normal tension glaucoma patients. RESULTS: In the supine position a statistically significant elevation of intraocular pressure was observed in 24 normal tension glaucoma patients by 6.2 +/- 2.8 mm Hg up to 21.8 +/- 3 mm Hg. Diastolic blood pressure in the supine position (80 +/- 10.5 mm Hg) was significantly lower than in the sitting position (94 +/- 11 mm Hg, p = 0.021). 12 of 28 normal tension glaucoma patients showed an intraocular pressure lower than 22 mm Hg in the supine position. In these patients a tendency towards a higher incidence for the occurrence of optic disc haemorrhages and significantly higher values for blood flow (p < 0.0005) and volume (p < 0.005) in the retina and optic nerve head could be shown. In this group of normal pressure glaucoma patients a higher incidence of migraine and vasospastic complaints was reported in the patients' history. CONCLUSION: In this study some normal tension glaucoma patients showed intraocular pressures in the supine position higher than 21 mm Hg and a lower diastolic arterial pressure. The higher incidence of haemorrhages and higher values for flow and volume parameters of the optic disc in normal tension glaucoma patients with an intraocular pressure lower than 22 mm Hg implicate the existence of two entities: real and pseudo normal tension glaucomas.     

The surgical treatment of normotensive glaucoma

The efficacy of surgical treatment of low (normal)-pressure glaucoma is validated on the basis of analysis of the disease progress risk factors. The risk factors are inadequate intraocular pressure (IOP) and insufficient blood supply to the optic nerve and retina. For stabilizing the glaucomatous process, IOP is to be reduced below 14 mm Hg. After antiglaucoma surgery, IOP decreases by 35% on average (to 13.9 mm Hg), and visual field is retained in remote period in 81.2% patients. Antiglaucoma operation with simultaneous decompression of the optic nerve results in a greater increase of visual field due to improvement of blood supply to the optic nerve and retina; visual functions are stabilized for a long time in 77.8% cases at a higher IOP (16.14 mm Hg) in patients with worse initial status. Functional results of surgery for normotensive glaucoma depend on ophthalmic tone and optic nerve and retinal hemodynamics.     

A quantitative study of nerve fibers in the human facial nerve

The facial and intermediate nerves were quantitatively evaluated in seven patients who died from systemic malignancies not involving the facial nerve. In addition, five of the specimens were also qualitatively evaluated by measuring the total and axon diameters of the facial and intermediate nerve fibers. In two cases the facial nerve fibers were counted at five different levels. The total number of myelinated nerve fibers in the facial nerve varied from 7500 to 9370. The total number of myelinated nerve fibers in the intermediate nerve varied between 3120 and 5360. The peak diameter of the facial nerve axon was between 4 and 6 microns, and was between 2 and 3 microns in the intermediate nerve. When comparing nerve segments at different anatomical levels, the largest amount of nerve fibers was found at the level of the middle mastoid portion. However, this number did not reach the amount of nerve fibers counted in the internal acoustic meatus.     

Evidence for glaucoma-induced horizontal cell alterations in the human retina

In this study we investigated changes to horizontal cells in human retinae affected by glaucoma. Glaucoma is characterized by raised intraocular pressure and is responsible for retinal ganglion cell and, possibly, photoreceptor degeneration. It was therefore assumed that horizontal cells might also be affected. The carbocyanine dye DiI was placed at discrete points on fixed, whole-mounted retinae obtained from normal and glaucomatous patients. After allowing 6-24 weeks for intramembranous diffusion within the lipid layers of the nerve cells and, therefore, fluorescent labeling, we measured horizontal cell soma and dendritic field sizes. Selected cells were then embedded in Araldite and cut at 4 microns. Horizontal cells in glaucomatous eyes appeared larger and had a granulated outline as compared with cells from normal retinae. Analysis of the mean cell soma size indicated that cells were 26% larger in the glaucomatous retinae and that this increase was significantly different from that seen in normal retinae (P < 0.05). The dendritic field size was unaffected (P > 0.05). As seen in cross section there was a clear loss of photoreceptor outer segments, and shrunken silhouettes of photoreceptor inner segments with pyknotic nuclei were observed. It is proposed that the increase in some size is indicative of horizontal cell responses that are likely to culminate in degeneration as a result of heightened intraocular pressure. In addition, this paper provides further evidence that photoreceptors are affected by advanced glaucoma.     

Differential in vivo effects of alpha-naphthoflavone and beta-naphthoflavone on CYP1A1 and CYP2E1 in rat liver, lung, heart, and kidney

Tenascin is a large extracellular matrix glycoprotein expressed in neural and non-neural tissues. In the central nervous system, tenascin is synthesized by astrocytes during development and wound healing, forming barriers and affecting neurite outgrowth. In this study we examined tenascin expression in optic nerve heads of normal and glaucomatous eyes and found that there is upregulation of tenascin mRNA and protein in reactive astrocytes from human glaucomatous optic nerve heads compared to normal age-matched controls. In the prelaminar region there was a band of tenascin immunoreactivity around the blood vessels of glaucomatous, but not in normal eyes. However, tenascin mRNA was only localized to astrocytes, suggesting that astrocytes are the cellular source of tenascin. In the lamina cribrosa, tenascin immunoreactivity and gene expression were localized to astrocytes in the cribriform plates and inside the nerve bundles. In the post-lamina region, tenascin immunoreactivity and gene expression were localized to astrocytes lining the pial septum immediately adjacent to the lamina cribrosa. In normal optic nerve heads, tenascin expression at the mRNA and protein levels was confined to clusters of astrocytes at the level of Bruch's membrane in the prelaminar optic nerve head. In glaucoma, enhanced expression of tenascin may be protective to the axons of the retinal ganglion cells by providing a barrier for humoral and/or blood-borne factors that may cause further neural damage. However, the precise role of tenascin in glaucomatous optic neuropathy is not yet elucidated.     

Parenteral anticholinergics in dogs with normal and elevated intraocular pressure

Dogs given parenteral anticholinergic drugs have been thought to be at risk for development or exacerbation of elevated intraocular pressure (IOP). In a randomized, blinded, placebo-controlled study, we evaluated the effect of intramuscular glycopyrrolate (0.01 mg/kg) on pupil diameter and IOP in unanesthetized normal dogs. Treatment with glycopyrrolate did not change pupil diameter or IOP from baseline, nor were there differences between glycopyrrolate and saline-treated (control) dogs. In addition, the authors retrospectively reviewed the medical records of 2,828 dogs undergoing general anesthesia between April 1987 and September 1990 to determine if there was an association between parenteral anticholinergic medication and postanesthetic elevation in IOP. The authors also determined the frequency of bradycardia requiring anticholinergic therapy during anesthesia in dogs with glaucoma. Of the 2,828 cases reviewed, the records of 46 dogs coded for glaucoma were examined in detail. The 46 dogs underwent 62 episodes of anesthesia, with 23 episodes including exposure to an anticholinergic drug. An increase in IOP from preanesthetic to postanesthetic measurement occurred in three dogs. One of these dogs received anticholinergic medication for bradycardia during anesthesia. The postanesthetic elevation in IOP in this dog was probably not drug related. Preanesthetic anticholinergic administration did not affect the incidence of anticholinergic administration for bradycardia during the anesthetic episode. Anticholinergic therapy during anesthesia was more frequent when the preanesthetic medication included an opiate drug. These studies do not indicate an association between parenteral anticholinergic administration and elevations in IOP.     

Changes in luminescence of the undiluted blood in patients with ischemic heart disease during laser therapy

AIMS: To examine the course taken by individual retinal ganglion cell axons through the human lamina cribrosa. METHODS: Retinal ganglion cell axons were labelled using the retrograde tracer horseradish peroxidase applied directly to the optic nerve in two normal human eyes removed during the course of treatment for extraocular disease. RESULTS: A majority of axons took a direct course through the lamina cribrosa but a significant minority, in the range 8-12%, deviated to pass between the cribrosal plates in both central and peripheral parts of the optic disc. CONCLUSIONS: It is postulated that these axons would be selectively vulnerable to compression of the lamina cribrosa in diseases such as glaucoma in which the intraocular pressure is increased.     

Glaucoma, capillaries and pericytes. 1. Blood flow regulation

Blood flow autoregulation may be deficient in patients with glaucoma, making the optic nerve circulation susceptible to the challenge of intraocular pressure (IOP). Adequacy or inadequacy of autoregulation may be a factor that decides whether a patient with elevated IOP develops glaucomatous optic nerve damage. Hypothetically, capillaries may assist arteries and veins in the regulation of blood flow. Our attention has become focused on the pericytes, particularly abundant in the optic nerve and retina, which are a contractile component of capillaries and may therefore be the cells responsible for the capillary's role in autoregulation.     

Long-term epinephrine therapy of ocular hypertension

Nineteen patients with symmetrical ocular hypertension and symmetrical cupping of the optic nerves were made asymmetric with respect to intraocular pressure for one to five years by unilateral topical treatment with epinephrine hydrochloride. Development of glaucomatous visual field defects was observed in 32% of the untreated eyes and in none of the treated eyes (P less than .05). Progressive cupping of the optic nerve was noted in 53% of the untreated eyes and in 11% of the treated eyes (P less than .025). Evidence of glaucomatous damage was observed more frequently in subjects maintained on this regimen for longer periods and in subjects with initial horizontal cup/disc ratios greater than 0.4 (P less than .05). None of the eyes, either treated or untreated, with mean intraocular pressures less than 24 mm Hg developed glaucomatous damage during the period of this study.     

Clinical and ocular histopathological findings in a patient with normal-pressure glaucoma

OBJECTIVE: To study the histopathological changes of eyes from a patient with normal-pressure glaucoma whose clinical and laboratory findings were well documented. METHODS: Postmortem histopathological findings in a patient with normal-pressure glaucoma who had monoclonal gammopathy and serum immunoreactivity to retinal proteins were examined in comparison with those of an age-matched control subject. Clinicopathological correlations to laboratory findings were examined. RESULTS: Clinical and histopathological findings of the patient, including cavernous degeneration of optic nerve and characteristic optic nerve cupping, were similar to those in patients with glaucoma who had high intraocular pressure. In addition, we found immunoglobulin G and immonuglobulin. A deposition in the ganglion cells, inner and outer nuclear layers of the retina, and evidence of apoptotic retinal cell death using terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling technique. CONCLUSIONS: Serum antibodies to retinal proteins and retinal immunoglobulin deposition constitute novel findings in a patient with normal-pressure glaucoma and may contribute to better understanding of the mechanisms underlying glaucomatous optic neuropathy in this disorder.     

Dyspnea in patients with chronic obstructive pulmonary disease: does dyspnea worsen longitudinally in the presence of declining lung function?

PURPOSE: The neurodegenerative progression of glaucoma is considered to be related not only to primary risk factors such as the elevation of intraocular pressure, but also to mediators of secondary neuronal degeneration. In the present study, the neuroprotective activity of the alpha2-adrenoreceptor agonists brimonidine, AGN 191103, and clonidine were examined in an animal model that simulates secondary neuronal degeneration of the optic nerve in a way thought to be independent of elevation of intraocular pressure. The beta-blocker timolol, currently used clinically to decrease intraocular pressure, was also examined for neuroprotective activity at dosages corresponding to the effective antihypertensive dosage. METHODS: A single dose of each of the tested compounds was administered intraperitoneally immediately after partial crush injury of the rat optic nerve. Secondary degeneration was measured by determining injury-induced deficits with and without the drug. This was achieved electrophysiologically by measurement of compound action potential amplitude, and morphometrically by counting the retrogradely labeled retinal ganglion cells, representing viable optic nerve axons, in wholemounted retinas. RESULTS: All three alpha2-adrenoreceptor agonists, but not timolol, exhibited neuroprotective effects. Treatment immediately after injury with each of these agonists resulted in a dose-dependent attenuation of the injury-induced decrease in compound action potential amplitude. Moreover, after treatment with 100 microg/kg brimonidine administered intraperitoneally, the loss of retinal ganglion cells 2 weeks after injury was three times lower than in saline-treated animals. CONCLUSIONS: In addition to their known effect of lowering intraocular pressure, alpha2-adrenoreceptor agonists, unlike timolol, exert a neuroprotective effect. Use of the rat optic nerve model of partial crush injury can serve as a method of screening compounds that are potentially capable of alleviating the progression of secondary neuronal degeneration.     

Nerve fiber layer defects with normal visual fields. Do normal optic disc and normal visual field indicate absence of glaucomatous abnormality?

PURPOSE: When the optic disc has normal appearance with no abnormalities in routine automated perimetry, the subject is not considered to have glaucoma. The purpose of this study is to show how such patients may have localized retinal nerve fiber layer defects with corresponding functional abnormality. METHODS: The authors selected eight eyes of eight patients who had a localized retinal nerve fiber layer defect extending within a few degrees from fovea but in whom the optic disc appearance and Humphrey 30-2 visual fields were normal. Of the eight patients, three had positive family history of glaucoma, two had suspected retinal nerve fiber layer abnormality in routine eye examination, two had increased intraocular pressure (IOP), and one had advanced low-tension glaucoma in one eye with a normal fellow eye. The authors examined the central 10 degrees visual field with 1 degree resolution using Humphrey perimeter and the Ring and Centring programs of the high-pass resolution perimeter. RESULTS: A central field defect corresponding to retinal nerve fiber layer defect was found in six of eight patients: in both 10 degrees Humphrey field and Centring programs (2 eyes), in Humphrey only (2 eyes), and in Centring only (2 eyes). CONCLUSION: The results indicate that retinal nerve fiber layer photographs are helpful in diagnosing glaucoma because early glaucomatous abnormalities cannot be excluded without nerve fiber layer photography. Currently available routine perimetric examination programs do not always detect very early functional damage.     

Action potential conduction and sodium channel content in the optic nerve of the myelin-deficient rat

Compound action potential (CAP) conduction and Na+ channel content were studied in optic nerves from control and myelin-deficient (md) rats. Action potential propagation was approximately five times slower in the md rat, but the action potentials propagated securely and had frequency-following and refractory properties equivalent to control myelinated axons. Tritium-labelled saxitoxin ([3H]-STX) binding in md optic nerve was approximately 30% greater, per wet mass of tissue, than in the control optic nerve. However, calculations of channel density per axon based on previously published anatomical data from md and control optic nerves (Dentinger et al. 1985) show an equivalent number of sodium channels per axon, with an average density of 10 channels micron-2 in md and 11 channels micron-2 in control optic nerve axons. The amplitude of the CAP in both control and md optic nerves was significantly attenuated by 50 nM TTX, precluding the possibility that TTX-insensitive channels are responsible for the action potential in myelinated or amyelinated axons. In addition, the amplitudes of voltage-activated Na+ currents in type I and type II astrocytes cultured from control and md optic nerves were similar, suggesting that the glial component of Na+ channels is not abnormal in the optic nerve of the md rat. These results suggest that myelination (or its absence) may not directly regulate the number of axonal Na+ channels.