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   Table of Contents      
ARTICLE
Year : 1983  |  Volume : 31  |  Issue : 5  |  Page : 535-537

Effect of therapeutic agents on acute ocular toxicity of methyl alcohol (An experimental study)


Dr. Rajendra Prasad Centre for Ophthalmic Sciences A.I.I M.S., New Delhi, India

Correspondence Address:
P K Khosla
Dr. Rajendra Prasad Centre for Ophthalmic Sciences A.I.I M.S., New Delhi
India
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Source of Support: None, Conflict of Interest: None


PMID: 6671751

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How to cite this article:
Khosla P K, Gupta A K, Tewari H K. Effect of therapeutic agents on acute ocular toxicity of methyl alcohol (An experimental study). Indian J Ophthalmol 1983;31:535-7

How to cite this URL:
Khosla P K, Gupta A K, Tewari H K. Effect of therapeutic agents on acute ocular toxicity of methyl alcohol (An experimental study). Indian J Ophthalmol [serial online] 1983 [cited 2019 Dec 15];31:535-7. Available from: http://www.ijo.in/text.asp?1983/31/5/535/36579

Table 1

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Table 1

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Toxicity of methanol is a subject of great significance and concern. Cases of methanol toxicity may increase in the future because of its endorsement as an important energy source of future and its extensive use in industry. Ever since the report of methanol induced blinding by Wood and Fuller in 1904, many reports have appeared in professional journals and lay newspapers indicating hundreds of deaths thus giving importance to the study of the toxicity of methanol. This article aims to study the efficacy of dexamethasone and xanthinol nicotinate in preventing acute ocular toxicity of methanol as studied in a suitable experimental animal model.


  Material and Methods Top


Healthy rhesus monkeys with no ocular disease, weighing 2.5 to 3.5 kg. were divided into 3 groups of six monkeys each. All animals were given methanol orally by intragastric Ryle's tube in a dose of 2G/kg. body weight. In group I (Methanol group) only methanol was given; in group II (Steroids group) dexamethasone monophosphate (Decadron) in a dose of 100 ug/kg/day intramuscularly was given in addition. In group III (Complamina group) xanthinol nicotinate (Complamina) in a dose of 15 mg/kg/day intramuscularly was given in addition. The control group received only Nembutol anaesthesia. Pupillary size and reaction to light, electro­-retinography, fundus photography, fundus fluorescein angiography and histopathology were carried on in each animal on first day (subgroup a) and on the third day (subgroup b) of the experiment.

Electroretinographs were recorded on Minograph 800 (Elma Schoender). The indigenously prepared corneal electrode and Grass photic stimulator was used with flash intensity at I 4 . Recordings were done at 3 parameter combinations (a) Speed 25 mm/sec. and sensitivity 500 uv/cm (b) Speed 25 mm/sec. and sensiti­vity 200 uv/cm. (c) Speed 50 mm/sec. and sensitivity 200 uv/cm.

Fluorescein angiography was done using Zeiss fundus camera. Sodium fluorescein was injected through femoral vein and serial photographs were taken including a late phase photograph at 15 ruts.

The anaesthesia used for all tests was Nembutol (sodium pentobarbitone) in a dose of 30 mg/kg. body weight intramuscularly.

Eyes were enucleated at the end of the experiment and histology was studied by light microscopy.


  Observations Top


The difference between the pupillary size in experimental animals when compared normal or within the experimental groups was statisti­cally insignificant (P/0.05). Only animals that died of methanol toxicity had a dilated and fixed pupils.

The results of electroretinography are summarised in [Table - 1]. There was no statistically significant change in 'a' wave amplitude in any of the subgroups as compared to normals or within the experimental groups (P/0.05) even when significant 'b' wave changes were present. 'b'wave was significantly lowered in methanol group (P/0.001) when compared to normal but intergroup differences were insignificant (P/0.05).

Blurring of the disc margins occurred along the superior inferior, temporal, and nasal margins in that order in the methanol group. Striate edema of the nerve fibre layer of the retina more along the major retinal vessels was seen which were confirmed on fluorescein angiography.

There were changes suggestive of oedema of the prelaminar part of optic nerve and the adjacent nerve fibre layer on histopathology. There was diffuse degeneration of various layers of the retina predominantly in the ganglion cells, but also involving the visual receptors and outer and inner nuclear layers.

There was reduction of edema in steroids group and diltation of vessels in complamina group.


  Discussion Top


Rhesus monkey has been chosen as the experimental animal because only in this animal acidosis and formatemia occurs following methanol administration [1] as in human beings because methanol is metabolised by enzyme hepatic ADH in both although a marked species difference in susceptibility to methanol exists [3] .

Corticosteroids were studied for their possible effect in reducing the optic disc edema which is a characteristic fundus finding in acute methanol toxicity. Xanthiol nicotinate was studied because attenuation of vessels is documented finding in methanol toxicity.

A suitable model of acute ocular toxicity of methanol for assessing effects of the therapeutic agents has been produced.

The findings of a decreased `b' wave in E.R.G., edema of the optic disc and peripapil­lary retinal nerve fibre layer as seen on fundus examination, fluorescein angiography and histopathology and the diffuse degeneration of the retina especially the ganglion cells characterise acute ocular toxicity of methanol.

In the present study `b' wave amplitude was decreased in the methanol as compared to normals. However, Karpe [1] had noted an increase in a wave amplitude and a decrease in `b' wave amplitude in the acute phase while Ruedman noted a decrease in both `a' and `b' waves and increase in mean latencies and Potts [3] noted normal a wave amplitude and extingui­shed `b' wave. The variability of electro-retino­graphic findings may depend upon a large number of factors like quantity ingested, metabolic status of the body, individual susceptibility, presence of other metabolites and the time and method of recordings.

The fundus and fluorescein angiographic findings of blurring of disc margins and striate edema of the nerve fibre layer are similar to those found in experimentally produced acute methanol toxicity in rhesus monkey [4] . However, he did not observe ocular changes after single dose of methanol as we did. We did not observe hyperaemia of optic disc, dilatation of veins, cherry red spot, dilatation of capillaries microaneurysms as our study was confined to 3 days only, it is difficult to comment whether these changes would have occurred later. The changes seen in our study are similar to stage I and II changes as described by Benton and Calhoun [5] . No arterial spasm as quoted by Duke Elder (1971) was noted. Our findings differ from Potts [3] who had described retinal edema starting in the papillomacular area and spreading both towards ora serrata and the optic disc.

Oedema of the prelaminar optic nerve and adjoining nerve fibre layer and diffuse degener­ation of retina especially the ganglion cells to a variable degree were seen on histQ­pathology. Degeneration of the ganglion cells has been described by a large number of authors [6],[7] to be the hallmark, however, Potts [3] found nuclei of ganglion cells to be normal. No polymorphonuclear infiltration was seen by us as demonstrated by Ealarson [8] . Our finding of degeneration of ganglion cells without atrophy of the optic nerve support the hypothesis that the optic atrophy is secondary to ganglion cell degeneration.

Presence of nearly similar changes as seen on fluorescein fundus angiography, ERG and histopathology after therapy are evidences to prove that dexametbasone and xanthionol nicotinate are ineffective in preventing acute ocular toxicity of methyl alcohol in experimental animals.


  Conclusions Top


A suitable model of acute ocular toxicity of methanol for assessing the effects of therapeutic agents has been produced. The findings of a decreased `b' wave in E.R..G., edema of optic disc and peripapillary retinal nerve fibre layer as seen on fundus examination, fluorescein angiography and histopathology and the diffuse degeneration of the retina especially the ganglion cells characterise acute ocular toxicity of methanol.

Two of the commonly used drugs-corticos­teroids and xanthinol nicotinate did not significantly decrease the acute ocular toxicity of methanol in the experimental model.

 
  References Top

1.
McMartin, K., Makar, A.B., Martin Arnat G., Palese, M., Tephly, T.R., Biochein. !Lied., 13, 319-333, 1975.  Back to cited text no. 1
    
2.
Ruedman, A.D., Amer. J. Ophthalmol., 54, 34-53, 1962.  Back to cited text no. 2
    
3.
Potts, A.M., Praglin, J., Farkcs, I., Amer. J. Ophthalmol., 40. 77-83, 1955.  Back to cited text no. 3
    
4.
Hayreh, M.M.S., Hayreh, S. S., Baumach, G.L., Cancilla, P., Martin Amat. G., Tephly T.R., McMartin, K.E., Makar, A.B., Arch. Ophtltal­mol., 95, 1851-1858, 1977.  Back to cited text no. 4
    
5.
Benton, C.D., and Calhoun, F.B., Trans. Am. Acad. Ophthalmol., 56, 875-883, 1952.  Back to cited text no. 5
    
6.
Fink, W.H., Amer. J. Ophthalmot., 26, 694-709, 802-815, 1943.  Back to cited text no. 6
    
7.
Roe, O., Acta Ophthalmol., 26, 169, 1948.   Back to cited text no. 7
    
8.
Ealarson, Acta !Lied. Scand., 117, 393, 1965.  Back to cited text no. 8
    



 
 
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