Indian Journal of Ophthalmology

: 1981  |  Volume : 29  |  Issue : 4  |  Page : 351--353

Effect of experimentally induced chronic copper toxicity on retina

DK Gahlot, KS Ratnakar 
 Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
D K Gahlot
Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi

How to cite this article:
Gahlot D K, Ratnakar K S. Effect of experimentally induced chronic copper toxicity on retina.Indian J Ophthalmol 1981;29:351-353

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Gahlot D K, Ratnakar K S. Effect of experimentally induced chronic copper toxicity on retina. Indian J Ophthalmol [serial online] 1981 [cited 2021 Jan 24 ];29:351-353
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For over two decades a vast number of retinotoxic agents are under investigation but these form a heterogenous group. Noell[1] drew attention to the close similarity between the iodoacetate induced retinal degeneration & human retinitis pigmentosa. However it is eommented that these retinal changes represent artificial situations unlikely to occur in life. Gahlot et al[2] showed that copper could induce degenerative changes in rabbit retina resem­bling retinitis pigmentosa.

A clinico-therapeutic trial has further indicated that human retinitis pigmentosa is possibly related to chronic copper toxicity due to some inherent metabolic defect.

In the present study a histological and electrophysiological correlation was tried by inducing copper toxicity.


A total of 12 pigmented rabbits weighing 1-1.5 kg. were used. They were fed on standard laboratory diet with water adlib, & kept under identical conditions of room temperature & illumination. Each rabbit was given 2 mg. copper sulphate solution by intraperiton_al injection each day. The experi­ments were terminated 2,4,6 & 8 weeks after copper administration. The eyes were enuclea­ted, fixed in neutral formalin and subjected to histopathology. The sections were stained with Haematoxylin & Eosin, Alcian Blue, Periodicacid schiff stain & Uzmans copper stains. Before beginning the experiment and each time before sacrificing the animal electro­retinography was performed under identical conditions on each animal on both eyes by using a suspended silver electrode making contact with the cornea through a cotton wick soaked in Saline. Two rabbits were kept as controls.


At the time of terminating the experiment ocular examinations did not reveal any abnormality. Fundus showed no vascular narrowing or pigmentary changes. Gross examination of the enucleated eyeballs showed no abnormality. Microscopic examination revealed changes localized in the retina. Other ocular structures were normal.

(A) 2 Weeks

The layer of rods and cones showed hydropic degeneration. No difference between rods and cones could be appreciated. In addition moderate separation of nerve fibre layer was seen. The nuclear layer and genglion cell were essentially preserved. The pigment epithelium showed no change. Electro­ retinography was normal. [Figure l]a.

(B) 4 Weeks

The hydropic degeneration of the receptor cell layer was more pronounced. Nuclear layers showed some irregularity. The pigment epithelium showed pigment fall out at various places. Electroretinography was extinguished. [Figure 1]b.

(C) 6 Weeks

The degeneration of photo receptor layer was advanced and the pigment epithelium showed focal thinning and migration of clumps of pigment towards the nuclear layers Electro­retinography was extinguished. [Figure 2].

(D) 8 Weeks:

The degenerative process of the rods & cones was further pronounced leading to their disappearance. Pigment epithelium showed marked changes. Focal discontinuity was seen at places along with migration of pigment in clumps at many places. It did not however reach deep down the nuclear layers. The vascular channels showed no abnormality.

There was no detachment of retina or other layers. No changes were seen either in the Bruchs, membrane or basement membrane of vascular channels. There were no inflamina­tory cells. The histological picture of (C) & (D) showed some overlap. The structural changes were not uniform, Same animals showed alteration of varying degrees in different parts of retina. [Figure 3] A&B

Electroretinography was extinguished.

Eversince Noell[1] Observed retinotoxicity following intravenous administration of iodoacetate a wide variety of organic & inorganic toxic agents have been investigated. Some of these include lodoacetic acid, Sodium Iodate, Sodium azide & Sodium glutamate. Valuable attempts were made to group these retinotoxic agents but majority of them formed a heterogenous group having little in common, structurally or metabolically. The histologic studies provide an exceptional oppor­tunity for the study of many problems con­cerning the relationship between retinal function and visual cell structure[3].

To corroborate biochemical findings sugges­ting a relationship between chronic copper toxicity & retinitis pigmentosa[2], a preliminary experimental study in rabbits by parenteral administration showed that copper was a potential retinotoxic agent. This study was significant because unlike other substancess, it represented a normal constituent of food and an important retinal metalloenzyme.

The results of present study show again that in pigmented rabbits analogous to primate pigmented eye, copper is capable of acting as a toxin to photoreceptor cells leading possibly to secondary changes in the pigment epithelium as seen by the migrating pigment clumps after 4 weeks of copper treatment. The structural damage of photoreceptor cells leads to functio­nal derangment of retina is substantiated by the extinction of electroretinogram in the 4 week group. This may: indicate that the func­tional changes probably precede gross structu­ral changes in the pigment epithelium. Thus there appears to be a positive correlation bet­ween copper toxicity and electroretinographic and histologic findings.


Chronic copper toxicity was produced in pigmented rabbits by injecting Copper Sulphate intraperitoneally. Electroretinography repea­ted after 4 weeks showed an extinguished res­ponse. Histologically retina showed degenera­tion of photo receptor cells and migration of pigment[4].


1Noel! W.K. 1951, J. Cell & Comp. Physiol. 37: 283.
2Gahlot D.K. Khosla P.K., Makashir P. D., Vasuki K. and Basu' N., 1976, Brit. J. Ophthalmol. 60:770.
3Noell W.K. 1953; Am. J. Ophthalmol. 36: 103,
4Graymore C.N. 1970 Biochemistry of the Eye 676, Academic Press, London.