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ORIGINAL ARTICLE
Year : 1983  |  Volume : 31  |  Issue : 2  |  Page : 65-68

Berberine : An indigenous drug in experimental herpetic uveitis


Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi-110029, India

Correspondence Address:
Madan Madan
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All-India Institute of Medical Sciences, New Delhi 110 029
India
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Source of Support: None, Conflict of Interest: None


PMID: 6662570

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How to cite this article:
Madan M, Sekhar G C, Mahajan V M. Berberine : An indigenous drug in experimental herpetic uveitis. Indian J Ophthalmol 1983;31:65-8

How to cite this URL:
Madan M, Sekhar G C, Mahajan V M. Berberine : An indigenous drug in experimental herpetic uveitis. Indian J Ophthalmol [serial online] 1983 [cited 2020 Oct 31];31:65-8. Available from: https://www.ijo.in/text.asp?1983/31/2/65/27439

Herpetic ocular disease is an important cause of ocular morbidity. The commonest ocular lesion produced by Herpes simplex virus is keratitis. Uveitis can also be produ­ced either primarily or in conjunction with keratitis. The treatment of herpetic stromal lesions and uveitis often poses many problems. Pavan-Langston[1] stated that attempts at therapy of herpetic uveitis with systemic and topical antivirals have been made and the results are encouraging but far from sati­sfactory and that the standard therapy of herpetic uveitis is aimed at suppressing the inflammatory reaction rather than eliminating the inciting agent. This study was undertaken to study therapeutic efficacy of berberine, sodium sulfacetamide and systemic sulfona­mide in different combinations against experi­mental herpetic uveitis.


  Materials and methods Top


Herpes virus type I was cultured in the Vero cells, both obtained from the Depart­ment of Microbiology, All-India Institute of Medical Sciences. Titrated virus having 10[4],[5] TCID 50 per ml was used as the inoculum.

A pilot study was conducted in which two rabbits and two guinea pigs were inocula­ted in the anterior chamber with 0.05 ml of HSV in the right eyes and the same amount of Eagle's MEM into the left eyes. The course of uveitis was observed clinically, microbiologically and histopathologically and the animal with a longer duration of uveitis was selected for further studies. At the height of uveitis, aqueous and iris were collected separately for viral isolation. Infected sheet was examined for cytopathic effect and intr­anuclear inclusions after staining with H & E stain. At the same time, rabbit was sacrificed, the eye enucleated and sections stained with haematoxylin and eosin were studied for histopathological changes. The rabbit was selected as the experimental animal.

Uveitis was studied in three groups of six animals each.

Group I : The animals were treated with local drops of sodium sulfacetamide 20%, three times a day and systemic sulfaphenazole (orisul) in a dose of 25mg/kg body weight for the first 10 days following the onset of uveitis.

Group 2 : The animals were treated with subconjunctival injections of 0.5 ml of 0.05% solution of berberine sulfate daily. The dose of berberine was decided after giving different doses sub-conjunctivally to exclude any toxic reaction of the drug per se.

Group 3 : The animals were treated with systemic sulfaphenazole as in ;group I and daily subconjunctival injections of berberine sulfate as in group 2.

In all the groups. the treatment was star­ted as soon as clinical signs of uveitis appeared and was continued till the active signs were present. The animals were examined daily with torch light and once in 3 days with Heigh-Streit-900 slit lamp. The severity of uveitis was graded from + to + + + + and the course recorded.


  Observations Top


The pilot study revealed that uveitis could he produced in both the animals as compared to the control eyes which showed only con­junctival congestion lasting for 2 days.

The inoculation of iris and aqueous samples into Vero-cells resulted in the produ­ction of cyto-pathic effect [Figure - 1]. The stained cells showed the presence of intranuclear inclusions.

The histopathological study revealed infla­nimation of the corneal endothelium, iris, ciliary body and angle region. with the cellular infiltrates consisting of lymphocytes, a few histiocytes and eosinophils. There were no giant or epitheloid cells [Figure - 2].

Berberine when given subconjunctivally in doses of 0.5 mg daily resulted in corneal vascu­larisation. marked conjunctival hyperaemia and bogginess. In a dose of 0.25 mg daily there was no undue reaction in the eye.

In both rabbits and guinea pigs. uveitis started by the second day. In rabbits, the severity of uveitis reached its peak by the 8th day, lasted through 8th to 10th day and sub­sided by the 15th day. In there animals uveitis was characterised by iris hyperaemia and moderate corneal oedema [Figure - 3]. In guinea pigs the peak of uveitis was reached by the 6th day and uveitis lasted till the 1Oth day. In these animals severe uveitis was characterised by corneal haze of a severe degree [Figure - 4]. Because of the pigmented nature of the ani­mals, iris hyperaemia was not discernible in the guinea pigs. As rabbit gave a longer course of uveitis which could be more easily clini­cally assessed, it was selected as an experi­mental animal.

In all the experimental groups, uveitis started by the 3rd day and reached its peak by 6th to 8th day. Uveitis subsided in all the groups by 12th day. The same course of uvei­tis was seen irrespective of the treatment given.


  Discussion Top


The pathogenesis of herpetic uveitis is not well established. Direct viral replication in the iris and anterior chamber and autoimmune factors have been considered. O'Connor[2] mentioned that the weight of evidence favours the proliferation of virus in the uveal tissue as a cause of inflammation in herpetic uveitis. The re-isolation of the virus from aqueous and iris samples in the present study lends support to this concept.

The histopathological study of uveitis re­vealed that the cellular response consisted of predominantly lymphocytes with few histio­cytes and occasional eosinophils. There were no epitheloid or giant cells. These findings confirm the clinical observations that herpetic uveitis, in rabbit., is of non-granulomatous type.

The drugs chosen for this study have never been tried against herpetic uveitis till to-date. A study of this sort was prompted by the following factors. Berberine has a wide range of antibacterial activity. It has been shown to inhibit RNA and protein synthesis[3],[4], forms a complex with DNA[5], has antitrachoma[3],[6],[8] and antimycotic[9] activity. Sulfa group of drugs have been the drug of choice in the treatment of trachoma and have also been shown to have in-vitro antimycotic Action[10].

In this study 0.5 ml of 0.05% berberine was used subconjunctivally daily. Verma[6] in clinical trials for trachoma used 0.1%, of solution at biweekly intervals. More frequent injections were reported to cause local granuloma and decreased absorption of the drug, No such complications were seen with the dose used in rabbits in this study. When given alone or in combination with systemic sulfonamide had no significant effect on uveitis. Local sodium sulfacetamide drops also did not significantly alter the course of uveitis in combination with systemic sulfona­mides.

Thus none of the drugs used could signifi­cantly affect the course of herpetic uveitis.

This study was undertaken to study the therapeutic efficacy of Berberine, sodium sulfacetamide and systemic sulfonamide in different combinations against herpetic uveitis. Uveitis was produced by anterior chamber inoculation of 0.05 ml HSV type I (TCID 50­10 4-5/ml). Comparison of course of uveitis so produced in rabbits and guinea pigs revealed that rabbit was a better experimental model. From the aqueous and iris samples of the inje­cted rabbits the virus could be reisolated. Histopathological study revealed the inflamm­ation of the non-granulomatous variety. Sulphacetamide drops (topical). sulfaphena­zole (svteniic) and berberine (subconjunctival) were found to be ineffective in treating ex­perimental uveitis.

 
  References Top

1.
Pavan Langston, 1975.. Amer..J. Ophthalmol. 30 : 495.  Back to cited text no. 1
    
2.
O'Connor, 1976, Lit. Ophthalmol. Clin. 15 (4). 89.  Back to cited text no. 2
    
3.
Modak S: Modak, M.J.: Venkataraman. A. 1970. Ind. .J.Med Res, 58:1510.  Back to cited text no. 3
    
4.
Amin. A.A, Subbaiah. T.V: Abbasi, K.M. 1969, Canad. .J. Microbiol. 15 : 1067.  Back to cited text no. 4
    
5.
Krey A.K: Hahn, F.E. 1969. Science 166 : 755.   Back to cited text no. 5
    
6.
Verma. R.L. 1933. Ind. Med. Gaz. 68 : 122.   Back to cited text no. 6
    
7.
Sabir M. 1975. Thesis. Ph.D. A.LLM.S.  Back to cited text no. 7
    
8.
Sabir. M; Mahajan. V.M. ; Mohapatra L.N. Bhide N.K., 1976. Ind..J Med. Res. 64 : 8.  Back to cited text no. 8
    
9.
Mahajan. V.M. : Sharma Anjana & Rattan Anita.. 1982, Sabouraudia 20 (1) : 79.  Back to cited text no. 9
    
10.
Mahajan. V.M., 1983, Mykosen 26 (2) :94.  Back to cited text no. 10
    


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]



 

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