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Screening method

Inactive Publication Date: 2004-01-22
TRIER KLAUS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0034] In accordance with the present invention it is however believed, that the substances in tha last end excerts the treating or preventing effect through an effect on the ion transport in and out of the cell in the retinal pigment epithelium and thereby exerts its effect on the longitudinal growth of the eye.
[0212] Significant higher content of all collagen specific amino acids, except hydroxylysine in anterior sciera, was found in all sclera samples from theobromine (3,7-dimethylxanthine) treated animals. Animals treated with 7-methylxanthine showed significantly higher content of hydroxyproline and proline in posterior sclera. Treatment with acetazolamide reduced the content of hydroxyproline and proline in anterior sclera significantly.10TABLE 10 Content of proteoglycanes in .mu.g PG / mg tissue (wet weight) anterior sclera posterior sclera Control 2.9 + / - 0.5 2.9 + / - 0.4 7-methyixanthine 2.5 + / - 0.5 3.3 + / - 0.3 3,7-dimethyixanthine 2.6 + / - 0.7 2.5 + / - 0.4 Acetazolamide 2.9 + / - 0.4 2.8 + / - 0.8 L-ornithine 3.0 + / - 1.1 3.0 + / - 0.9 Anterior sclera Posterior sclera Increase Decrease Increase Decrease 7-methylxanthine -- 14% 14% --3,7-dimethylxanthine -- 10% --14% Acetazolamide -- -- -- --L-ornithine -- -- -- --

Problems solved by technology

The intermediary form,and the excessive one in particular, is connected to a high risk of severe sight threatening complications such as e.g. retinal detachment, degenerative changes in the yellow spot of the eye (macula degeneration) and glaucoma.
In order to justify a medical treatment of these conditions, such treatment must be effective at relatively low dosages and roughly without any side effects, accordingly, as application of VIP, dopaminergic, anticholinergic or tricyclical substances is connected to risk of side effects as, simultaneously, the substances have considerable psychochemical effects these prior art substances are not suitable for such treatment.
Thus it is been shown possible to trigger irreversible stretching of the sclera in young rabbits by increasing the intraoccular pressure but it is not possible to stretch the sclera in mature rabbits (Greene, P. R., ARVO Abstracts, 1978, p.
However, tests with reduction of the intraoccular pressure by means of beta-blocking eye drops in humans developing myopia have no effect (Jensen, H., Acta Ophthalmol., Suppl.
Furthermore, in chicken the sclera is considerably anomalous as it partly consists of cartilage.

Method used

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Examples

Experimental program
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Effect test

example 1

[0160] Materials and Methods

[0161] Test animal: Charles River Deutschland Chinchilla Bastard female rabbits.

[0162] Number of animals: 6 test animals and 6 control animals

[0163] Age: approximately 8 weeks at the commencement of the test.

[0164] Weight: 1.4-1.9 kg at the commencement of the test.

[0165] Lightness / Darkness cycle: 12 / 12 hours.

[0166] Water: ad libitum.

[0167] Cages: The animals live in identical cages made of stainless steel-(Scanbur), length 1 m, depth 0.52 m, height 0.5 m.

[0168] Food: Stanrab standard diet from Special Diet Services, P.O. Box 705, Witham Essex CM8 3AD, UK (further details, see Table A).

[0169] Amount of food: Increasing from 75 g per day at the commencement of the test up to 130 g after three months.

[0170] Experimental drinking water 1 contained theophyllin in a dose equivalent of 27 mg increasing to 63 mg (added as theophyllin and ethylendiamin in a dose of 33 to 77 mg) daily.

[0171] Experimental drinking water 2 contained fluoxetine (Fontex, Lilly) in a d...

example 2

[0193] Long time treatment of 3 month with each of the four substances, Caffeine, L-cysteine, Teofylamin, and Fluoxetine and the effect on the biochemical changes in rabbit sclera

5TABLE 5 Content of collagen specific amino acicis in nanomol / mg tissue (dried weight defatted weight) from anterior sclera (Wilcoxon test. *p < 0.05), and the increase (Inc.) or decrease (Decr.) compared to the control. Hydroxyproline Hydroxylysine Proline Control 604 + / - 50 41 + / - 12 886 + / - 29 Fluoxetine 619 + / - 40 33 + / - 11 896 + / - 21 Teofylamin 653 + / - 39 28 + / - 10 958 + / - 23 Caffeine 688 + / - 36* 39 + / - 19 993 + / - 18* L-cystine 599 + / - 41 45 + / - 10 885 + / - 22 Hydroxyproline Hydroxylysine Proline Inc. Decr. Inc. Decr. Inc. Decr. Fluoxetine -- -- -- 20% -- --Teofylamin 8% -- -- 32% 8% --Caffeine 14% -- -- -- 12% -- L-cystine -- -- -- -- -- --

[0194]

6TABLE 6 Content of collagen specific amino acids in nanomol / mg tissue (dried weight and defatted weight) from posterior sclera (Wilcoxon test.), and the incre...

example 3

[0201] Myopia progression stopped by treatment with caffeine and L-cystine

[0202] A boy presented with myopia at the age of 9 years. Earlier examination showed no ametropia. He had severely progrediating myopia and was treated with a combination of caffeine (100 mg / day) and L-cystine (200 mg / day) for three months followed by a control period of three months with no treatment, and subsequently a new treatment period followed by a control period, etc. In total 4-treatment periods and 4 control periods alternated.

[0203] Measurement of the axial length of the eye was made by means of Auto Axial Biometer AL-010, Shin-Nippon.

[0204] Table 8 and Table 9 shows the average growth in the axial length of both eyes in the 4 treatment periods and the 4 control periods, respectively.

8TABLE 8 Treatment with caffeine 50 mg .times. 2 and L-cystine 100 mg .times. 2 (tablets) from day 0-90, day 161-289, and 412-570. Day RE LE 0 23.74 23.70 57 23.86 23.58 118 24.06 23.83 161 24.14 24.07 227 24.21 24.03 2...

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Abstract

The invention relates to a method for identification of substances which are applicable for treatment or prevention of an insufficient longitudinal growth of the eye (hypermetropia) or for treatment or prevention of an excessive longitudinal growth of the eye (myopia); substances identified by the method for treating or preventing conditions related to the longitudinal growth of the eye; substances and mixtures of substances for the preparation of a pharmaceutical composition for the treatment or prevention of abnormal growth of the axial length of the eye. The identification involves measuring the effect of the substances on the retinal pigment epithelium of the eye, e.g. by detecting the metabolic effect of the substance on the retinal epithelium, the effect on the standing potential or the effect on the proteoglycanes of the scleral tissue of the eye, by way of EOG examination, by way on the size of the so-called c-wave in ERG-recordings, or by the state of the Ca<2+>-channels or on the [<3>H]-ryanodine receptors of the retinal pigment epithelium.

Description

[0001] The invention relates to a method for identification of substances which are applicable for treatment or prevention of an insufficient longitudinal growth of the eye (hypermetropia) or for treatment or prevention of an excessive longitudinal growth of the eye (myopia); substances identified by the method for treating or preventing conditions related to the longitudinal growth of the eye; substances and mixtures of substances for the preparation of a pharmaceutical composition for the treatment or prevention of abnormal growth of the axial length of the eye.[0002] Myopia is caused by the length of the eye being too big in relation to the optical strength of the cornea and the lens so that the picture of a distant object is focused in a point in front of the retina, whereas the picture produced on the retina will be blurred. In other words, myopia is caused by an anomaly between the length of the eye (the axial length) and the refraction in the cornea and the lens.[0003] The lo...

Claims

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Application Information

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IPC IPC(8): A61K31/00A61K31/13A61K31/138A61K31/196A61K31/198A61K31/382A61K31/428A61K31/433A61K31/4422A61K31/522G01N33/50
CPCA61K31/00G01N33/5088A61K31/138A61K31/196A61K31/198A61K31/382A61K31/428A61K31/433A61K31/4422A61K31/522G01N33/5008G01N33/502G01N33/5044G01N33/5058A61K31/13A61P27/02
Inventor TRIER, KLAUS
Owner TRIER KLAUS
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