Indian Journal of Ophthalmology

: 1959  |  Volume : 7  |  Issue : 2  |  Page : 39--42

The effect of citral on variations in the aqueous outflow facility of rabbits

Hamida Saiduzzafar 
 M. U. Institute of Ophthalmology, Aligarh, India

Correspondence Address:
Hamida Saiduzzafar
M. U. Institute of Ophthalmology, Aligarh

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Saiduzzafar H. The effect of citral on variations in the aqueous outflow facility of rabbits.Indian J Ophthalmol 1959;7:39-42

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Saiduzzafar H. The effect of citral on variations in the aqueous outflow facility of rabbits. Indian J Ophthalmol [serial online] 1959 [cited 2021 Apr 16 ];7:39-42
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Citral is a substance which in nature is found in the oil of lemon-grass and in the peel of oranges and lemons. Therefore it is present in certain articles of diet wherein the peel of citreous fruit is eaten, e.g. marmalade and lime-pickles.

Leach and Lloyd of Oxford while working on experimental glaucoma in monkeys found that some of their control animals which were receiving oranges in their diet exhibited raised intra-ocular pressure. They considered the citral of the orange-skin to be the toxic substance responsible, and further investigated it from this point of view. In rabbits they found that citral in doses as low as 5 µ.g./kg. of body-weight causes raised intra-ocular tension. They further observed that the toxic effect of citral was greater in the presence of a Vitamin A deficiency. This, they stated, indicated that citral which in structure resembles the aldehyde retinene, ( the precursor of Vitamin A) acts as a competitor for retinene in the cells of the trabecular mesh-work ( Moore 1957 ).

In a large series of observations on rabbits we were unable to demonstrate any rise in intra-ocular tension with citral, even with doses as high as 26 mgm. per rabbit, and neither was there any significant alteration in the facility of outflow.

Now according to Eric Linn& of Sweden (1958) very early glaucomatous changes may not be detected by tonometry or tonography alone. It has been known for some time that Acetazoleamide ( Diamox ) reduces the rate of aqueous flow (Becker 1955), therefore Linner has devised a changeability test of aqueous outflow resistance which would detect the earliest variations from normal. This test depends on the fact that pilocarpine increases the facility of outflow, whereas drugs like Diamox reduce it. The coefficient of facility of outflow as measured by Tonography, C, is expresssd as The initial facility of outflow C 1 of the untreated eye gives a reference point for the facilities found with Pilocarpine and Diamox respectively, and the changes can be expressed as three ratios :

P/I, D/I and P/D respectively.

P - facility of outflow with Pilocarpine.

D - facility of outflow with Diamox.

I - initial facility of outflow.

METHOD : We treated four groups of rabbits as follows:-

GROUP I : Heavily citralised over 4months, with no Vitamin A in the diet.

GROUP II : No Vitamin A in the diet.

GROUP III : Normal controls.

GROUP IV : Citralised, but no normal diet.

Tonography was performed by the Mueller Electronic Tonometer, tracings being obtained on the Sanborn Recorder. A special holder devised and made in our workshop was used to keep the tonometer steadily on the eye for 4 minutes. For more accurate and uniform analysis the Right eye readings alone were considered, and the 5.5.G weight was used throughout [Figure 1].

Tonography was done initially. Then Pilocarpine 3% was instilled into the right eye, twice at intervals of one hour, and tonography repeated an hour after the second instillation. After an interval of at least 48 hours Diamox 125 mgm./lb. of body-weight, was administered orally by stomach-tube; two such doses were given at 4-hourly intervals. Tonography was then performed 4 hours after the second dose. The coefficients of facility of outflow were statistically analysed in terms of the three ratios P/I, D/I and P/D respectively so that the effect of Citral and Vitamin A deficiency on the capacity to vary the outflow resistance could be studied.


[Table 1] shows the P/I, D/I, and P/D values obtained from the right eye of the 22 rabbits in the four experimental groups. Separate analysis of variance was carried out on these values to find out whether the variations in the means indicated any real effect or were wholly accounted for by errors of random sampling. The three analysis of variance are given in [Table 2],[Table 3],[Table 4] . It will be seen from these tables that the error mean square is consistently larger than that between means square, and conse­quently there is no question of the significance of the F. ratio. It follows that there is no evidence to indicate that the four groups are differing in the values P/I, D/I or P/D. In other words, the rabbits which were on citral with or without Vitamin A deficiency (Groups I, II, IV) did not differ from the normal rabbits (Group III), in their aqueous outflow facility.

The actual mean values of the variates P/I, D/I and P/D in the four groups are given in [Table 5], together with the appropriate standard errors. Here we find that in all the groups the mean values for D/I are low, whereas those for P/I are higher. This indicates that Diamox increases the resistance to outflow and reduces the facility of outflow while Pilocarpine has the opposite effect.

[Table 5] further shows that the ratio P/D gives the highest value : this is as one would expect, because this is the ratio which indicates the total range of variation produced by the two drugs Pilocarpine and Diamox respectively.


Our results indicate that the rabbits were responsive in that they showed the expected variations in their capacity to vary the outflow resistance. However, Citral did not affect this phenomenon in any significant manner.

In another series of experiments we had already found that Citral did not produce any significant changes in the intra-ocular tension of the four experimental groups of rabbits.

If Citral could have been used to reproduce experimental glaucoma, we could perhaps have reversed its effect with Vitamin A. This drug might thus have been used to make further studies as to mechanism involved in ocular hypertension.

Unfortunately, however, we were unable to find any evidence of rise in tension or reduction in facility of outflow with Citral over a wide range of dosage.

The changeability test of Linner when applied to the four groups of rabbits likewise showed no significant alteration in the ratios.

Therefore we have not been able to find any evidence that Citral is a factor in the etiology of glaucoma. Recently, Lennart Bergren of Sweden has obtained similar results with citral; using the Schiotz tonometer he found that Citral had no effect on the intra-ocular tension of rabbits.[5]


1Becker, B., (1955) A.M.A. Arch. Ophthal., 54, 321.
2Becker, B., (1 957) A.M.A. Arch. Ophthal., 58, 871.
3Bergren, L., Acta Ophthal., 35.5.
4Leach, E.H., & Lloyd, J.P.F., Trans. O.S.U.K., 76, 453.
5Linner, E (1958) Brit. J.Opthal.,52,38.