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   Table of Contents      
ARTICLE
Year : 1983  |  Volume : 31  |  Issue : 5  |  Page : 545-547

Retinotoxic effect of zinc, manganese and molybdenum on rabbit retina (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: 6671755

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How to cite this article:
Khosla P K, Karki D B, Gahlot D K. Retinotoxic effect of zinc, manganese and molybdenum on rabbit retina (An experimental study). Indian J Ophthalmol 1983;31:545-7

How to cite this URL:
Khosla P K, Karki D B, Gahlot D K. Retinotoxic effect of zinc, manganese and molybdenum on rabbit retina (An experimental study). Indian J Ophthalmol [serial online] 1983 [cited 2019 Aug 25];31:545-7. Available from: http://www.ijo.in/text.asp?1983/31/5/545/36583

The study has been undertaken to study the retinotoxic effect of zinc, manganese and moly­bdenum on rabbit retina.


  Materials and Methods Top


A total of 36 healthy adult albino rabbits weighing between 1.25 to 1.65 kg. were taken and kept in the same environment of temperature, illumination and diet. Before the start of the experiment each animal was examined clinically including a fundus examination ERG was done. Anaesthesia used as nembutol in the dosage of 33 mg/kg body weight given intravenously. 4% topical xylocaine drops were also used. The animals were divided into control group consisting of nine animals and test groups consisting of 27 animals (nine for each element). They were further divided into three subgroups, consisting of three animals each of which were sacrificed at 2 weeks, 4 weeks and 8 weeks.

Zinc as zinc sulphate 0.5%, manganese as man­ganese sulphate 0.2% and molybdenum as sodium molybdate 0.2%, were administered intraperitioneally in the doses of 1ml. on alternate days in the test animals. In the control groups, sodium chloride 0.9% was given by the same route.

At the end of two, four or eight weeks a detailed clinical examination and ERG was repeated with identical parameters. Eyes were enucleated for histo­pathology.


  Observations Top


Clinically no abnormal ocular findings were observed in either control or test groups besides general signs of toxicity in test groups.

Control group: No changes were observed both in ERG and histopathology.

Test Group I (Zinc)

Highly significant decrease in `a' wave (P<0.001) and total ERG (P<0.01) was seen in the 8 week group, while in the 4 week group, only `a' wave decreased (P<0.05).

Time related focal histopathological changes i.e. hydropic degeneration of photoreceptors with initial degeneration in inner segment, migration of nuclei of outer nuclear layer into the degenerated area of photoreceptors and cystic degeneration of ganglion cell layer were seen.

Test Group II (Manganese)

A significant decrease in `a' wave (P<0.001), increased in `b' wave (P<0.001), but decrease in total ERG in the 8 week group (P<0.05) was seen.

Almost similar focal histological changes were seen akin to the zinc group.

Test Group III (Molybdenum)

'Time related highly significant decrease in `a' wave, `b' wave and total ERG (P<0.001) was seen.

Focal histopathological changes, similar to the other two groups were seen except that the degeneration was relatively more pronounced in this group.


  Discussion Top


Zinc, manganese and molybdenum are among essential trace elements having close inter-relationship not only within themselves but also with others like copper and lead. They play an important role in cellular activity particularly of retina due to their association with various metallo-enzymes and metal activated enzymes. It is known that an important connection exists between pigment metabolism and copper (Underwood, 1956) which is related to other trace elements. It is likely, therefore, that the deficiency or excess of not one trace element but of various elements together that brings about derangement in the cellular process.

In the present study no abnormal clinical ocular findings including fundus findings were detected.

In zinc toxicity significant decrease in `a' wave and total ERG in the 8 week group, correlated well with histopathological changes seen in the photoreceptors.

A somewhat similar finding was observed in manganese group also. The changes were time related. However in this group an increase in `b' wave found in the 8 week group is difficult to explain.

In molybdenum group the ERG changes were seen right from 2 weeks but as the duration of toxicity increased, ERG and histopathological changes became more advanced.

Histopathologically degenerative changes were mainly localised in the photoreceptors. Two interesting findings seen were cystic degeneration of ganglion cells and migration of nuclei of outer nuclear layer into degenerated areas of photoreceptors in the zinc and molyb­denum treated groups. No changes were seen on light microscopy in the retinal pigment epithelium.

Noell [1] has reported similar finding with iodoacetate. Other retino-toxic substances like sodium fluoride (Orzalisi, 1970), Urethan (Bellhorn) [2] , Fenthium (Miyata et al) [3] etc. have also been reported similar ERG and histological changes. There is, however, no common basis for the biochemical or toxic effect of these agents but the elements studied by us are dietary essentials and vital to all living things.

A high zinc content in chorio-retina in the rabbit eye (Weitzel, 1968) and relationship between zinc and retinal mechanisms is well known (Halstead and Smith) [4] . Reading (1970) shows that zinc was necessary for maintaining normal level of Vitamin A in the body and a decrease in retinal alcohol dehydro­genase activity is seen in association with zinc levels. Hughes and Coogan [5] explained lead induced retinopathy by the inhibitory action of lead on zinc dependent enzyme system. Role of zinc in the metabolism of retina is further strengthened by the report of a pigmentary degeneration of retina induced by Dithizone which is a zinc precipitating agent (Sorsby, 1958). The role of zinc in cellular metabolism particularly of DNA and RNA has been emphasized recently by Prasad et al [6] . In the present study also retino-toxicity of zinc is likely to be directly or indirectly related to the inhibition of enzymatic system involved in the metabolism of retina.

Similarly manganese toxicity may result either due to direct toxic effect on the retina or indirectely by its relationship with other trace elements as excessive manganese is known to result in decreased concentration of copper in plasma (Gubler, 1954).

Molybdenum is functionally related to copper. Dick (1956) and Bowen (1966) have emphasized the complexity of molybdenum­copper interrelationship. It has been observed that while high manganese intake can block the limiting effect of molybdenum on copper retention (Dick, 1956), molybdenum restricts copper utilisation (Mills, 1961) and Molybde­num toxicity results in copper deficiency [7] .


  Summary Top


Zinc, manganese and molybdenum are all potentially retino-toxic elements having a selective effect on photoreceptors and ganglion cells. Of the three elements studied molybdenum is found to be the most toxic.

 
  References Top

1.
Noell, W.K., J. Cell Comp. Physiol., 37,283,1951.  Back to cited text no. 1
    
2.
Bellhorn, R.W., Bellhorn, M.J., Friedman, A.W. & Henkind, P., Inv. Ophthalmol., 12, 65, 1973.  Back to cited text no. 2
    
3.
Miyata, M., Imai, H.S., Ishikawa, S., Proc. Of XXIII Int. Cong. Oph. Kyoto, 901, 1978.  Back to cited text no. 3
    
4.
Halstead, and Smith, J.E., Gastroenterology, 67, 193, 1974.  Back to cited text no. 4
    
5.
Hughes, F., and Coogan, P.S., Amer. J. Pathol., 77, 237, 1974.  Back to cited text no. 5
    
6.
Prasad, Ananda S., Trace Elements in human Health and Disease Vol. eds. Prasad and Obevleas, 1976.  Back to cited text no. 6
    
7.
Underwood, E.J., Trace Elements in Human and Animal Nutrition: Second edition, 1962.  Back to cited text no. 7
    




 

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