|Year : 1979 | Volume
| Issue : 4 | Page : 170-173
Retinitis pigmentosa-A state of copper toxicity ?
R.P. Centre for Ophthalamic Sciences, New Delhi, India
D K Gahlot
R.P. Centre for Ophthalamic Sciences, New Delhi- 16
|How to cite this article:|
Gahlot D K. Retinitis pigmentosa-A state of copper toxicity ?. Indian J Ophthalmol 1979;27:170-3
Retinitis pigmentosa is a primary degeneration of the retina which startes in early life and gradually progresses to total blindness. Its aetiology is unknown and it has often been considered an abiotrophy.
It is well known that an important relationship exists between copper and pigment formation in the body. Since in the classical disease of retinitis pigmentosa, pigment disturabance in the equatorial region of the retina is an outstanding feature, a relationship between copper and retinitis pigmentosa was postulated and a study of copper metabolism in these patients was undertaken. A report of this study is presented in this paper.
| Materials and Methods|| |
Fifteen patients of retinitis pigmentosa between the ages of 10 and 50 years were investigated. The diagnosis was based on the history of progressive night blindness not responding to conventional treatment; and on fundus picture showing consecutive optic atrophy, attenuated blood vessels and pigment dispersal of a varying degree and was confirmed by subnormal or flat electro retinographic and electrooclulo graphic response.
These cases were thoroughly investigated and other causes of retinal pigmentary degeneration like tuberculosis and syphilis were rulel out. They were then subjected to the following three biochemical tests.
1. Total serum copper determined by the method of Ventura and Kings as modified by Varley.
2. Caeruloplasmin level in plasma determined in terms of its copper oxidase activity in optical density (O.D.) units using the method of O'Brien and Ibbott(17). Due precautions were taken to avoid contamination by siliconizing the glassware used for the purpose.
3. Copper excertion in urine determined by the method of Gubler et a1 as modified by Henry. Ten normal subjects were taken as control for each of these tests.
The results have shown that the total serum concentration in normal subjects varied from 60 to 150 ug/100 ml of serum while that in patients with retinitis pigmentosa varied from 36 to 108 ug/100 ml of serum. The statistical analysis showed that the mean value of serum copper in these patients was not significant at 5 per cent level although individually some of them had figures lower than normal. [Figure - 1].
The caeruloplasmin concentration in optical density units in normal subjects ranged from 0.19 to 0.31 (mean 0.23) while that in patients ranged from 0 03 to 0.36 (mean 0.118). This showed that the concentration of caeruloplasmin in the plasma of pigmentosa patient was significantly lower, (P/0.001). [Figure - 2].
The copper excretion in urine in normal subjects ranged from 0-50 ug/24 hours while the urinary excretion in patients with retinitis pigmentosa varied from 15-400 ug/24 hours (mean 215). This indicated that there is a very striking and highly significant increase in the excretion of copper in these patients (P/0.001). [Figure - 3].
| Discussion|| |
Copper forms an important constituent of most food stuffs and is considered an indispensable trace element for the body. An average daily adult diet contains about 2-5 mg of copper which is mainly excreted through the bowels.
According to Cartwright (1950) an adult human body contains a total of 100-150 mg of copper most of which is present in plasma in the bound form as caeruloplasmin. The mean plasma concentration of copper in Americans and Europeans is about 100 ug/100 ml (range (75-160 ug/100 ml).,,, This figure corresponds well with the figure obtained in the normal controls of our series and the copper serum concentration in the patients with retinitis pigmentosa although had a mean figure lower than normal, it was not considered significant at 5 per cent level.
Copper metabolism in the body seems particularly sensitive and is seen to undergo changes in several clinical conditions. Most chronic infections, myocardial infarction, hepatitis, portal cirrhosis, hyperthyroidism and malignant conditions etc. lead to hypercupreamia while hypocupraemia is known to occur mainly in nephrotic syndrome and hepato-lenticular degeneration. It is also observed that the condition of hyper or hypocupraemia is associated with increased or decreased caeruloplasmin concentration respectively because a major part of copper in the body exists as a component of caeruloplasmin. Caeruloplasmin in an alphagloublin responsible for the oxidase activity of blood which in turn varies with the serum copper levels. Scheinberg believes that caeruloplasmin plays an important role in the maintenance of zero copper balance in the body.
The results of this study showing a near normal serum copper concentration, low caeruloplasmin concentration and a greatly increased urinary copper excretion in the patients of retinitis pigmentosa are significant firstly because they have never been reported in relation to this disease and secondly they have been described only in relation to hepatolenticular degenration, a condition of chronic copper toxicity. Thus it may be concluded that inspite of widely different clinical presentations there is a possibility that hepatolenticular degeneration and retinitis pigmentosa may in some way be related and that retinitis pigmentosa may also be a state of chronic copper toxicity.
This hypothesis as the aetiological factor in retinitis pigmentosa was then put to a therapeutic test by putting five of these patients on a copper chelating agent Penicillamine widely used in hepatolenticular degeneration.
The following schedule was observed:
I) Low copper diet containing about I mg copper daily, II) 40 mg potassium sulphide capsule, one with each meal, III) Pyridoxine 25 mg tablet per day and IV penicillamine (cuprimine) 250 mg capsules starting from two capsules a day, increasing gradually to eight capsules a day, During therapy a close watch was kept on the appearance of allergic and other adverse reactions and a regular blood count and urine tests were conducted to monitor the haematological and copper excretion state. The results of follow up (22 months in cases I & 2, 18 months in case 3, 12 months in case 4, and 6 months in case 5), show that all the patients improved in their visual status both as regards visual acuity and visual fields. However the degree of improvement seemed to be limited by the degree of macular damage already present. [Figure - 4],[Figure - 5],[Figure - 6],[Figure - 7].
Thus on the basis of the biochemical and therapeutic evidences presented here it may be concluded that retinitis pigmentosa may be a condition of chronic copper toxicity possibly due to inborn error of copper metabolism.
| References|| |
|1.||Cartwright G.E., 1950, 'Copper metabolism' eds W .D. |
|2.||McElooy & B. Glass, 274, John Honkins, Baltimore. |
|3.||Gubler, C.J., 1956, J. Amer. Med. Ass. 161, 530. |
|4.||Gubler C.J. Lahey M.E, Aschenbruker H., Cartwrogjt G.E. & Wintrobe M.M., 1952, J. Biol. Chem., 196, 209. |
|5.||Henry, R.J., 1968, clinical Chemical Principles & Techniques Harper & Row, New York. |
|6.||Markowitz, H. Gubler C.J., Mahoney J.P., Cartwright G.E. & Wintorobe M.M., 1955, J. Clui. Invest , 34, 1498. |
|7.||O'Brien D. & Ibbott, F.A., 1964, Laboratory Manual of Paediatric Micro & ultra micro. Biochemistry 3rd ed. Harper & Row, New York. |
|8.||Scheinburg, H.I., 1966, Biochemistry of Copper ed. J. Peisach, P. Aisen & W.E. Blumberg, 518, Academic Press, London. |
|9.||Scheinberg H.I. & Sternlieb, 1960, Pharcol. Rev., 12,355. |
|10.||Underwood, E.J., 1956, Trace Elements in Human & Animal Nutrition, 77, Academic Press, New York. |
|11.||Ventura S. &King E.J., 1951, Biochem. J., 48, 66. |
|12.||Varley, H., 1975, Practical Clinical Biochemistry 4th ed., 479, Arnold-Heinemann. India. |
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7]