2
O c u l a r D e g e n e r a t i o n Ocular Restoration System A powerful antioxidant. Immediately neutralizes free radicals and is a glycosylation and protein crosslinking inhibitor. The most important, powerful antioxidant in the lens. Critical in protecting protein, DNA repair. Antioxidant, detoxifying activity. Helps stabilize cell membrane, modulation of cellular calcium levels. N-Acetyl L-Carnosine L-Carnosine Glutathione L-Taurine Riboflavin Cysteine Ascorbate A water soluble vitamin (B-2). Vital for the synthesis and recycling of Glutathione. A water stable source of vitamin C and L- cysteine, necessary for matabolism of Glutathione. Provides the same activity as L-Carnosine but with longer residence time in the cells. T h e S y s t e m s A p p r o a c h K e y I n g r e d i e n t s i n O c l u V e t s P a t e n t - P e n d i n g F o r m u l a Glycation a of lens proteins is a primary factor in cataract formation 1,2,3 . Glycation results in the formation of a Schiff base (SB) b and Amadori rearrangement c via the Maillard reaction d leading to early glycation products. As the process continues, dehydration and rearrangement leads to cross-links between adjacent proteins, resulting in protein aggregates, advanced glycation end products (AGE’s) and increased oxidative stress (glycoxidation) 4, 5, 6 . In simple terms, with age, disease, or trauma the crystallin proteins in the eye lens are damaged and denatured allowing them to “clump” together. This clumping of damaged proteins is what is recognized as a cataract. a glucose or other reducing sugars react with the e-amino group of lysine residues or amino terminal (n-terminal) of proteins b an organic compound in which the nitrogen (N) atom of an amino group is doubly bonded to a carbon (C) atom c a rearrangement that occurs in cross-linking reactions seen in protein glycosylations d one of a group of nonenzymatic reactions in which aldehydes, ketones or reducing sugars react with amino acids, peptides or proteins 1 Yan H, Willis AC, Harding JJ. Gamma III-crystallin is the primary target of glycation in the bovine lens incubated under physiological conditions. Biochem J. 2003; 374, 677-85. 2 Beswick HT, Harding JJ. Conformational changes induced in lens alpha and gamma-crystallins by modification with glucose 6-phosphate, implication for cataract. Biochem J. 1987; 246, 761-69. 3 Sell DR, Monnier VM. The conversion of arginine into ornithine by advanced glycation in senescent human collagen and lens crystallins. J Biol Chem 2004; 279, 54173-84. 4 Biemel KM, Friedl DA, Lederer MO. Identification and quantification of major maillard cross-links in human serum albumin and lens protein. Evidence for glucosepane as the dominant com- pound. J Biol Chem 2002; 277, 24907-15. 5 Jansirani, Anathanaryanan PH. A comparative study of lens protein glycation in various forms of cataract. Indian Journal of Clinical Biochemistry, 2004. 19; 110-112. 6 Watkins NG, Thorpe SR, Baynes JW. Glycation of amino groups in protein. Studies on the specificity of modification of RNase by glucose. J Biol Chem, 1985. 260, 10629-36. 7 Monnier VM, Cerami A. Nonenzymatic browning in vivo: possible process for aging of long-lived proteins. Science, 1981. 211, 491-3. O v e r v i e w Crystallin lens proteins are long-lived proteins 7 expressed early in life with virtually no turnover or protein synthesis. The eye protects its DNA from damage with numerous antioxidant systems. The OcluVet formula was designed to target the reactions that lead to the formation of damaged proteins and provide the nutrients needed to repair the altered amino residues and oxidation to allow the proteins to return to their healthy, noncross-linked state. Unlike oral or commercially available eye drop supplements that demonstrate little or no benefit, OcluVet utilizes a systems approach targeting compromised and damaged components of the eye. This powerful antioxidant/nutrient system provides immediate neutralization of existing free radicals and is a glycation and protein cross-linking inhibitor. MIDWEST VETERINARY SUPPLY

Ocular Degeneration Clinical Studies - midwestvet.net · Ocular Degeneration Ocular ... Conformational changes induced in lens alpha and gamma-crystallins ... Two clinical trials

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Ocular Degeneration

Ocular Restoration System

A powerful antioxidant. Immediately neutralizes free radicals and is a glycosylationand protein crosslinkinginhibitor.

The most important, powerful antioxidant in the lens. Critical in protecting protein, DNA repair.

Antioxidant, detoxifying activity. Helps stabilize cell membrane, modulation of cellular calcium levels.

N-AcetylL-CarnosineL-Carnosine GlutathioneL-Taurine Riboflavin

CysteineAscorbate

A water soluble vitamin (B-2). Vital for the synthesis and recycling of Glutathione.

A water stable source of vitamin C and L-cysteine, necessary for matabolism of Glutathione.

Provides the same activity as L-Carnosinebut with longer residence time in the cells.

The Systems Approach

Key Ingredients in OcluVet’s Patent-Pending Formula

Glycationa of lens proteins is a primary factor in cataract formation1,2,3. Glycation results in the formation of a Schiff base (SB)b and Amadori rearrangementc via the Maillard reactiond leading to early glycation products. As the process cont inues , dehydra t ion and

rearrangement leads to cross-links between adjacent proteins, resulting in

protein aggregates, advanced glycation end products (AGE’s) and increased

oxidative stress (glycoxidation)4, 5, 6. In simple terms, with age, disease, or trauma the crystallin proteins in the eye lens are damaged and denatured allowing them to “clump” together. This clumping of damaged proteins is what is recognized as a cataract.

aglucose or other reducing sugars react with the e-amino group of lysine residues or amino terminal (n-terminal) of proteins

ban organic compound in which the nitrogen (N) atom of an amino group is doubly bonded to a carbon (C) atom

ca rearrangement that occurs in cross-linking reactions seen in protein glycosylations done of a group of nonenzymatic reactions in which aldehydes, ketones or reducing

sugars react with amino acids, peptides or proteins

1Yan H, Willis AC, Harding JJ. Gamma III-crystallin is the primary target of glycation in the bovine lens incubated under physiological conditions. Biochem J. 2003; 374, 677-85. 2Beswick HT, Harding JJ. Conformational changes induced in lens alpha and gamma-crystallins by modification with glucose 6-phosphate, implication for cataract. Biochem J. 1987; 246, 761-69. 3Sell DR, Monnier VM. The conversion of arginine into ornithine by advanced glycation in senescent human collagen and lens crystallins. J Biol Chem 2004; 279, 54173-84. 4Biemel KM, Friedl DA, Lederer MO. Identification and quantification of major maillard cross-links in human serum albumin and lens protein. Evidence for glucosepane as the dominant com-

pound. J Biol Chem 2002; 277, 24907-15. 5Jansirani, Anathanaryanan PH. A comparative study of lens protein glycation in various forms of cataract. Indian Journal of Clinical Biochemistry, 2004. 19; 110-112. 6Watkins NG, Thorpe SR, Baynes JW. Glycation of amino groups in protein. Studies on the specificity of modification of RNase by glucose. J Biol Chem, 1985. 260, 10629-36. 7Monnier VM, Cerami A. Nonenzymatic browning in vivo: possible process for aging of long-lived proteins. Science, 1981. 211, 491-3.

Overview

Clinical Studies

David L. Williams and Patricia Munday Dept. of Veterinary Medicine, University of Cambridge Madingley Road, Cambridge, CB3 OES, England, UK

These photographs are of a U. S. study participant (patient 185). The photo on the left is pretreatment and the photo on the right is at 8 weeks post-treatment. The supervising veterinarian noted that at the 6 and 8 week exams the retinal vessels were visible where previously they could not be seen. This is clearly demon-strated in the photos.

Multi-Veterinary Clinic U.S. Study

6

80

14

23

123

6

71

916

102

0

95 7

21

0

20

40

60

80

100

120

140

Lenticular Sclerosis(100%)

Immature Cataract(89%)

Hypermature Cataract(64%)

Misc. Cataract (70%)

Total All Eyes (83%)

# Eyes TreatedMeasurable Reduction No Change

SUMMARY Animals studied 64 animals of varying species, breeds and ages with a spectrum of lens opacities ranging from lenticular sclerosis to hypermature cataract. Methods Patients were treated three times daily with topical n-acetyl-carnosine, l-carnosine, glutathione, cysteine ascorbate, l-taurine and riboflavin in a buffered lubricating solution. Animals were examined prior to treatment and at 4, 6 and 8 weeks during treatment, by ophthalmoscopy and varying tests of visual responsiveness including owner observations.

Multi-Veterinarian/Multi-Veterinary Clinic Study Data gathered from 23 hospitals in different geographical locations across the United States.

SUMMARY Animals studied 30 dogs of varying breeds and ages with a spectrum of lens opacities ranging from nuclear sclerosis to total mature cataract. Methods Dogs were treated three times daily with topical 2% N-acetyl carnosine in a buffered vehicle containing the antioxidants glutathione, cysteine ascorbate, L-taurine and riboflavin (OcluVet™, Practivet, Phoenix, AZ, USA). Dogs were examined prior to treatment and at 2, 4 and 8 weeks during treatment, by direct and indirect ophthalmoscopy and slit-lamp biomicroscopy after pharmacologic pupil dilation.

Dr. David Williams, University of Cambridge

14 13

21

9

57

1412

14

7

47

0 1

7

2

10

0

10

20

30

40

50

60

Nuclear Sclerosis(100%)

Immature Cataract(92%)

Mature Cataract(66%)

Misc. Cataract (77%)

Total All Eyes (82%)

# Eyes TreatedMeasurable Reduction No Change

Two clinical trials have been completed to test the OcluVet formulation in patients with lens opacities ranging from lenticular sclerosis to hypermature cataract. One trial was conducted by a researcher at the University of Cambridge, Dr. David L. Williams, MA VetMB PhD CertVOphthal MRCVS (results published 9/2006 Veterinary Ophthalmology). He reported that 47 of the 57 eyes (82%) showed a measurable reduction in opacity. He also notes that owner evaluation of visual capability suggested improvement in vision in 80% of cases. The second was a multi-hospital U.S. study and the supervising veterinarians reported 102 of the 123 eyes (83%) studied showed a measurable reduction in opacity. The similar findings between both studies is remarkable. The superior results seen in the earlier stages of cataracts and lenticular sclerosis indicates a significant benefit in beginning administration of OcluVet at the first sign of any opacity. It should also be noted that in hypermature cases administration of 1 drop TID for a period longer than 8 weeks may increase the reduction seen in these latter stages.

Crystallin lens proteins are long-lived proteins7 expressed early in life with virtually no turnover or protein synthesis. The eye protects its DNA from damage with numerous antioxidant systems. The OcluVet formula was designed to target the reactions that lead to the formation of damaged proteins and provide the nutrients needed to repair the altered amino residues and oxidation to allow the proteins to return to their healthy, noncross-linked state. Unlike oral or commercially available eye drop supplements that demonstrate little or no benefit, OcluVet utilizes a systems approach targeting compromised and damaged components of the eye. This powerful antioxidant/nutrient system provides immediate neutralization of existing free radicals and is a glycation and protein cross-linking inhibitor.

MIDWEST VETERINARY SUPPLY

Ocular Degeneration

Ocular Restoration System

A powerful antioxidant. Immediately neutralizes free radicals and is a glycosylationand protein crosslinkinginhibitor.

The most important, powerful antioxidant in the lens. Critical in protecting protein, DNA repair.

Antioxidant, detoxifying activity. Helps stabilize cell membrane, modulation of cellular calcium levels.

N-AcetylL-CarnosineL-Carnosine GlutathioneL-Taurine Riboflavin

CysteineAscorbate

A water soluble vitamin (B-2). Vital for the synthesis and recycling of Glutathione.

A water stable source of vitamin C and L-cysteine, necessary for matabolism of Glutathione.

Provides the same activity as L-Carnosinebut with longer residence time in the cells.

The Systems Approach

Key Ingredients in OcluVet’s Patent-Pending Formula

Glycationa of lens proteins is a primary factor in cataract formation1,2,3. Glycation results in the formation of a Schiff base (SB)b and Amadori rearrangementc via the Maillard reactiond leading to early glycation products. As the process cont inues , dehydra t ion and

rearrangement leads to cross-links between adjacent proteins, resulting in

protein aggregates, advanced glycation end products (AGE’s) and increased

oxidative stress (glycoxidation)4, 5, 6. In simple terms, with age, disease, or trauma the crystallin proteins in the eye lens are damaged and denatured allowing them to “clump” together. This clumping of damaged proteins is what is recognized as a cataract.

aglucose or other reducing sugars react with the e-amino group of lysine residues or amino terminal (n-terminal) of proteins

ban organic compound in which the nitrogen (N) atom of an amino group is doubly bonded to a carbon (C) atom

ca rearrangement that occurs in cross-linking reactions seen in protein glycosylations done of a group of nonenzymatic reactions in which aldehydes, ketones or reducing

sugars react with amino acids, peptides or proteins

1Yan H, Willis AC, Harding JJ. Gamma III-crystallin is the primary target of glycation in the bovine lens incubated under physiological conditions. Biochem J. 2003; 374, 677-85. 2Beswick HT, Harding JJ. Conformational changes induced in lens alpha and gamma-crystallins by modification with glucose 6-phosphate, implication for cataract. Biochem J. 1987; 246, 761-69. 3Sell DR, Monnier VM. The conversion of arginine into ornithine by advanced glycation in senescent human collagen and lens crystallins. J Biol Chem 2004; 279, 54173-84. 4Biemel KM, Friedl DA, Lederer MO. Identification and quantification of major maillard cross-links in human serum albumin and lens protein. Evidence for glucosepane as the dominant com-

pound. J Biol Chem 2002; 277, 24907-15. 5Jansirani, Anathanaryanan PH. A comparative study of lens protein glycation in various forms of cataract. Indian Journal of Clinical Biochemistry, 2004. 19; 110-112. 6Watkins NG, Thorpe SR, Baynes JW. Glycation of amino groups in protein. Studies on the specificity of modification of RNase by glucose. J Biol Chem, 1985. 260, 10629-36. 7Monnier VM, Cerami A. Nonenzymatic browning in vivo: possible process for aging of long-lived proteins. Science, 1981. 211, 491-3.

Overview

Clinical Studies

David L. Williams and Patricia Munday Dept. of Veterinary Medicine, University of Cambridge Madingley Road, Cambridge, CB3 OES, England, UK

These photographs are of a U. S. study participant (patient 185). The photo on the left is pretreatment and the photo on the right is at 8 weeks post-treatment. The supervising veterinarian noted that at the 6 and 8 week exams the retinal vessels were visible where previously they could not be seen. This is clearly demon-strated in the photos.

Multi-Veterinary Clinic U.S. Study

6

80

14

23

123

6

71

916

102

0

95 7

21

0

20

40

60

80

100

120

140

Lenticular Sclerosis(100%)

Immature Cataract(89%)

Hypermature Cataract(64%)

Misc. Cataract (70%)

Total All Eyes (83%)

# Eyes TreatedMeasurable Reduction No Change

SUMMARY Animals studied 64 animals of varying species, breeds and ages with a spectrum of lens opacities ranging from lenticular sclerosis to hypermature cataract. Methods Patients were treated three times daily with topical n-acetyl-carnosine, l-carnosine, glutathione, cysteine ascorbate, l-taurine and riboflavin in a buffered lubricating solution. Animals were examined prior to treatment and at 4, 6 and 8 weeks during treatment, by ophthalmoscopy and varying tests of visual responsiveness including owner observations.

Multi-Veterinarian/Multi-Veterinary Clinic Study Data gathered from 23 hospitals in different geographical locations across the United States.

SUMMARY Animals studied 30 dogs of varying breeds and ages with a spectrum of lens opacities ranging from nuclear sclerosis to total mature cataract. Methods Dogs were treated three times daily with topical 2% N-acetyl carnosine in a buffered vehicle containing the antioxidants glutathione, cysteine ascorbate, L-taurine and riboflavin (OcluVet™, Practivet, Phoenix, AZ, USA). Dogs were examined prior to treatment and at 2, 4 and 8 weeks during treatment, by direct and indirect ophthalmoscopy and slit-lamp biomicroscopy after pharmacologic pupil dilation.

Dr. David Williams, University of Cambridge

14 13

21

9

57

1412

14

7

47

0 1

7

2

10

0

10

20

30

40

50

60

Nuclear Sclerosis(100%)

Immature Cataract(92%)

Mature Cataract(66%)

Misc. Cataract (77%)

Total All Eyes (82%)

# Eyes TreatedMeasurable Reduction No Change

Two clinical trials have been completed to test the OcluVet formulation in patients with lens opacities ranging from lenticular sclerosis to hypermature cataract. One trial was conducted by a researcher at the University of Cambridge, Dr. David L. Williams, MA VetMB PhD CertVOphthal MRCVS (results published 9/2006 Veterinary Ophthalmology). He reported that 47 of the 57 eyes (82%) showed a measurable reduction in opacity. He also notes that owner evaluation of visual capability suggested improvement in vision in 80% of cases. The second was a multi-hospital U.S. study and the supervising veterinarians reported 102 of the 123 eyes (83%) studied showed a measurable reduction in opacity. The similar findings between both studies is remarkable. The superior results seen in the earlier stages of cataracts and lenticular sclerosis indicates a significant benefit in beginning administration of OcluVet at the first sign of any opacity. It should also be noted that in hypermature cases administration of 1 drop TID for a period longer than 8 weeks may increase the reduction seen in these latter stages.

Crystallin lens proteins are long-lived proteins7 expressed early in life with virtually no turnover or protein synthesis. The eye protects its DNA from damage with numerous antioxidant systems. The OcluVet formula was designed to target the reactions that lead to the formation of damaged proteins and provide the nutrients needed to repair the altered amino residues and oxidation to allow the proteins to return to their healthy, noncross-linked state. Unlike oral or commercially available eye drop supplements that demonstrate little or no benefit, OcluVet utilizes a systems approach targeting compromised and damaged components of the eye. This powerful antioxidant/nutrient system provides immediate neutralization of existing free radicals and is a glycation and protein cross-linking inhibitor.

___________________________________________________Midwest Veterinary Supply

Burnsville, MN Sun Prairie, WI Des Moines, IA Fort Wayne, IN Valley Forge, PA Owings Mills, MD1-800-328-2975 1-800-362-9226 1-800-643-9378 1-800-447-7496 1-800-583-8020 1-800-583-8020