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ARTICLES
Year : 1981  |  Volume : 29  |  Issue : 1  |  Page : 29-34

Effect of hyperosmotic agent (mannitol) on ciliary epithelium


Dr. Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, India

Correspondence Address:
P K Khosla
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, A.I.I.M.S, New Delhi 110029
India
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Source of Support: None, Conflict of Interest: None


PMID: 6793512

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How to cite this article:
Khosla P K, Nayak B K, Prakash P, Ratnakar K S. Effect of hyperosmotic agent (mannitol) on ciliary epithelium. Indian J Ophthalmol 1981;29:29-34

How to cite this URL:
Khosla P K, Nayak B K, Prakash P, Ratnakar K S. Effect of hyperosmotic agent (mannitol) on ciliary epithelium. Indian J Ophthalmol [serial online] 1981 [cited 2020 Oct 26];29:29-34. Available from: https://www.ijo.in/text.asp?1981/29/1/29/30987

Table 1

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Table 1

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The effect of hyperosmotic solutions in reducing intraocular and intracranial pressure has been known since the turn of the century. But the exact mechanism of action is still not well understood.

Various mechanisms like the opening up of blood aqueous barrier,[1] increase in the blood osmolarity and decrease in vitreous volume and weight[2],[3] have been described. In addition, certain structural changes also have been described[4],[5],[1], but the reports regarding the struc­tural changes are conflicting and there is no study available in which the effects of hyperos­motic agents were studied to rule out the possible changes produced by low intraocular pressure on ciliary epithelium.

This study was undertaken to see the changes in the ciliary epithelium using the most com­monly used hyperosmotic agent, i.e. Mannitol about which no other study is available.


  Materials and methods Top


Twenty-six pigmented rabbits were divided in the following groups

Group I (4 eyes) the control group for the histopathological parameters.

Group II (16 eyes)

Subgroup II A
(8 eyes) The rabbits were given single dose (2 gm/kg body weight) of intravenous 20% Mannitol in a dose of a rate of 70-80 drops/minute. The intraocular tension was recorded before injection and then at the interval of 10 minutes, 30 minutes, 1 hour, 4 hours and 6 hours. Four eyes were enucleated after one hour and the remaining 4 eyes after 6 hours of injection of mannitol.

Subgroup If B (8 eyes) The rabbits were given three consecutive doses (2 gm/kg body weight) of 20% mannitol intravenously at 8-hourly interval and the intraocular tension was recorded and eyes examined histopatholo­gically in the same manner as in Group II-A.

Group III (16 eyes)

Subgroup III-A (8
eyes) Treated like sub­group IT-A.

Subgroup III-B (8 eyes) Treated like sub­group II-B.

(In both the subgroups the intraocular ten­sion was maintained at normal level[6])

Group IV (16 eyes)

Subgroup IV-A (8
eyes) Single paracentesis was done and eyes were examined in the same manner as in group II-A.

Subgroup IV-B (8 eyes) Three consecutive paracentesis were done at the interval of 8 hours, and eyes examined in the same manner as in group II-B.


  Observations Top


Intraocular tension

It was seen that after each does of mannitol the intraocular tension started falling after 10 minutes and the maximum fall was noted from half an hour to one hour. It started rising in 4 hours period and became normal in 6 to 8 hours period [Figure - 1] &{Figure 2].

It is noted that immediately after each paracentesis the tension became unrecordably low and it started rising after one hour and in 4 to 6 hours period, it became normal [Figure - 3],[Figure - 4]


  Histopathology Top


Similar changes were noted in the eyes enucleated 1 hour and 6 hours after the injec­tion of mannitol.

The changes were noted in ciliary epithelium [Figure - 5] & [Figure - 6] in groups II-A and II-B. The pig­ment epithelium showed damage and dispersal of pigment and at places the pigment was lying free in the stroma. The pigmented epithelium showed separation from the non-pigmented epithelium at various places.

The non-pigmented epithelium did not show much change. It seemed that these are not damaged although appearances of vacuoles was present. The ciliary body stroma showed congestion of the blood vessels.

In groups III-A and III-B, in which the intraocular pressure was maintained at the pre-mannitol level, the changes were similar as in groups II-A and II-B except the congestion of blood vessels which was less marked [Figure - 7]. After paracentesis there was no change in ciliary epithelium except the congestion of blood vessels [Figure - 8]. [Table - 1] shows the changes in ciliary epithelium in various sub-groups.


  Discussion Top


All the hyperosmotic agents are supposed to lower the intraocular pressure by producing a rapid increase in blood osmolarity, which produces an osmotic gradient between blood and ocular fluids, resulting in loss of water from the eye to the hyperosmotic plasma.

In the present study in group II the intrao­cular tension, became normal in six to eight hours period whereas Okisaka et al[4] have described that after intracarotid injection of urea and lactamide it took three to six weeks for the intraocular pressure to become normal again. This difference is obviously due to the hyperosmotic agent and difference in the route of administration which goes in a bolus form after intracarotid injection must be causing some long-lasting disturbance in secretory mechanism which took three to six weeks period to become normal. We do not expect the osmotic gradient to be maintained between blood and inner ocular fluids for such a long period, so believe that there must be some other mechanism involved in lowering of the intraocular pressure than the osmotic effect alone which can be its effect on secretary mechanism. In the present study while giving repeated intravenous mannitol injection at eight hourly interval, it was noted that after each dose the intraocular tension became nor­mal in six to eight hours period. This indi­cates that the mannitol as the hyperosmotic agent dose not have that long-lasting hypoten­sive effect as is with intracarotid injection of urea and lactamide.

The damage of pigment epithelium noted in this study supports the similar observations made elsewhere[4],[5]. The damage to the pigment epithelium may be due to mannitol itself or my be due to the lowered intraocular pressure. However, the later possibility has been ruled out by obtaining the constant intraocular pres­sure to pre-mannitol level after giving mannitol in group III experiments and in this group damage to pigment epithelial layer was also noted. In group IV, only paracentesis was done and the intraocular tension was brought down and this group showed no such damage of pigment epithelium which clearly indicates that the damage in pigmented epithelial layer is due to direct effect of mannitol and not due to lowered intraocular pressure as it was seen whenever mannitol was given irrespective of the intraocular pressure

Hyperosmotic agents can cause reduction of vitreous volume and weight.[3] This decrease in vitreous volume and intraocular pressure may be due to either withdrawing more fluid from the inner chamber to the outside of eye or may be due to decreased secretion or may be the both.

Why does only the pigment epithelium show damage? One possible explanation may be the close proximity of pigment epithelial cells to the ciliary capillaries. These capillaries are rela­tively more permeable, and mannitol might cause increase in the permeability by altering the pores of these capillaries which has also been noticed after intracarotid hyperos­motic agents.(9) The demonstration of damage of pigment epithelium in this study indicates that mannitol has got some effect on the secre­tary mechanism as well, because the aqueous is secreted by the ciliary epithelium.

The appearance of vacuoles in the cytoplasm of the non-pigmented epithelium cells in the present study was also thought to be due to the effect of mannitol itself. These vacuoles denote that there is alteration in transport mechanism across the ciliary epithelium. Although on light microscopy, integrity of the nonpigmented epithelial cells was observed to be maintained. It is likely that eventually small amounts of osmotically active molecules of relatively large size are able to circumvent the blood aqueous barrier mechanism and vacuoles may be playing some part. Some authors have made similar observation as far as blood brain barrier is concerned indicating that it can be opened up without light micro­scopic damage to the cells, however, this is in sharp contrast to the destruction of the ciliary non-pigment epithelium after intracarotid injec­tion of urea[1] who concluded that non-pig­mented epithelium of the blood aqueous barrier is more susceptible to osmotic shock and resultant damage than is the blood-brain barrier. It appears that the intravenous use of hyperosmotic agent, which is used therapeu­tically poses almost no threat to the integrity of ciliary nonpigmented epithelium.

Separation of pigmented epithelial cells from nonpigmented epithelial cells at places also denotes some alterations in permeability of blood aqueous barrier.

The evidence of damage of pigmented epithelial cells, appearance of vacuoles in the non-pigmented epithelial cells and at places separation of pigmented epithelium from the non-pigmented epithelium in this study indi­cates that the intravenous use of mannitol in therapeutic doses does affect the blood aqueous barrier to some extent.


  Summary Top


The effect of intravenous hyperosmotic agent (mannitol) on ciliary epithelium was studied by histopathological examination under light microscope in rabbits. Main changes noted were the damage of pigmented epithelial cells, appearance of vacuoles in the nonpig­mented epithelium cells and at places separa­tion of pigmented epithelium from non-pigmented epithelial cells. On this basis it is sur­mised that mannitol has some effect on the secretory mechanism of aqueous and the blood aqueous barrier[7].

 
  References Top

1.
Shabo, A.L. Maxwell, D.S. and Kreiger, A.E. 1976, Amer. J. Ophthalmol. 81 :162.  Back to cited text no. 1
    
2.
Bucci, M.G. and Virno, M., 1968, Bull. Ocu­list., 47:407.  Back to cited text no. 2
    
3.
Agarwal, L.P., Deb, R.K. and Khosla, P. K. 1973, East, Arch. Ophthalmol. 1 : 319.  Back to cited text no. 3
    
4.
Okisaka, S., Kuwabara, T. and Rapoport, S.I., 1973, Science, 184: 1298.  Back to cited text no. 4
    
5.
Okisaka, S.; Kuwabara, T. and Rapoport, S.I. 1976, Invest. Ophthalmol. 15 : 617.  Back to cited text no. 5
    
6.
Hamasaki, D.I. and Fujino, T., 1967, A.M.A. Arch. Ophthalmol. 78 : 369.  Back to cited text no. 6
    
7.
Brightman, M.W., Hon.M., Rapoport, S.I., Ruse, T.S. and Wesergard, E., 1973, J. Comp. Neurol., 152: 317.  Back to cited text no. 7
    


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8]
 
 
    Tables

  [Table - 1]



 

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