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Ortho Eyes

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Ortho Eyes

$68.45 CAD

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AOR CODE: AOR04249

Protects the Eyes Against Cataracts

  • Reduces glare associated with laser eye surgery

  • Improves visual clarity 

  • Eye drops backed by clinical research

Use this product for: Eye Health AOR Uniques
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Details

Ortho Eyes contains N-acetyl-carnosine, a dipeptide (a combination of two amino acids) known to help reduce damaged, dysfunctional proteins called AGEs (advanced glycation end-products). AGEs render tissues dysfunctional, resulting in various health problems, particularly in the eyes. Studies have demonstrated that topical N-acetyl-carnosine eye drops alleviate eye tiredness, improve vision, reduce cataract severity, relieve corneal dystrophy, hasten recovery from corrective eye surgery and prevent corneal haze formation after cataract surgery. For the first time, a non-surgical treatment is available for those whose vision is slowly fading behind the curse of lens opacities, the most common cause of treatable blindness and the reason behind 1.3 million US operations per year - the most common surgical procedure in the elderly. 

Ortho Eyes is a unique eye drop formula that is a revolutionary and natural solution for aging eyes. The active ingredient, N-acetyl-L-Carnosine, is better absorbed than regular carnosine and is extremely effective when applied directly to the eye as an eye drop. Ortho Eyes may help improve the vision of those with cataracts, age-related macular degeneration and possibly other eye disorders. Those about to undergo cataract surgery or laser eye surgery can recover more quickly and fully with the help of Ortho Eyes. Ortho Eyes may also benefit those with aging eyes and those with healthy eyes who want to keep them that way.

Label Info

Discussion

Helps reduce glare and improves visual acuity against age related effects such as cataracts. 

Product Variation

Product Code NPN Size
AOR04249 80024426 2 VIALS 5 ML

Supplements Facts

Serving Size: Amount % Daily
N-Acetyl-carnosine (NAC) 1.0 %

Inactive Ingredients : sterile water (opthalmic grade isotonic solution pH 6.3 to 6.4), glycerin (lubricant), citric acid, boric acid, hypromellose, potassium bicarbonate, benzyl alcohol (preservative).

Adult Dosage

Instill 2 drops in each eye twice per day, or as directed by a qualified health care practitioner. Wash hands with water and soap for at least 30 seconds. If you wear glasses or contact lenses remove them. Lean head back and look up, if you have neck problems, lie down or use a tilt-back chair. With the eyes open, gently pull the lower eyelid below the eyelashes away from the eye. Instill “one drop”, then slowly and gently close the eye, being careful not to squeeze the eye drop out of the eye. Do not blink or reopen for 60 seconds. Repeat this procedure, if a second drop is used. Closing the eye allows each drop to be absorbed into the eye tissue.

Cautions

To avoid contamination, do not touch tip of the container to your eyes or any other surface. Replace the cap immediately after using. Open only one container of solution at a time. Do not allow other people to use your container. Once open, discard container and any contents after 30 days. Do not heat beyond room temperature; keep the extra container in the box away from light, especially sunlight. Do not use if seal is broken or if solution changes colour or becomes cloudy. Not recommended for children under the age of 12. Application may cause temporary irritation of the eye. If the eye tissue becomes more inflamed, red, irritated or uncomfortable after using this product, or if the condition worsens or persists for more than 72 hours, discontinue use and consult a physician. Keep this and all drugs out of the reach of children. Use before expiration date marked on container.

Source

Pharmaceutical synthesis

Main Application

Eye health

Cataracts

Disclaimer

The information and product descriptions appearing on this website are for information purposes only, and are not intended to provide or replace medical advice to individuals from a qualified health care professional. Consult with your physician if you have any health concerns, and before initiating any new diet, exercise, supplement, or other lifestyle changes.

Research

Background

N-Acetyl-Carnosine Eye Drops: A Revolution in Orthomolecular Eye Health!

The excitement surrounding the dipeptide Carnosine began when researchers at the Commonwealth Scientific and Industrial Research Organization (CSIRO), Australia’s premier scientific research center painstakingly documented the unthinkable: that carnosine can not only slow down, but actually reverse, cellular senescence – the process of “aging” at the cellular level. Based on their results, scientists “propose that carnosine is an important component of cellular maintenance mechanisms,” and “favor the view that it may have a very important role in controlling cellular homeostasis” – that is, in keeping cells in the tightly-regulated condition that optimizes their function.

Taking Out the Trash

But how Carnosine exerts these effects remains a mystery. In test-tube studies, Carnosine protects cells and biomolecules against a sweeping range of toxic insults. The one protective effect that’s probably received the most attention in the life extension community is its ability to protect proteins against glycation – the process through which sugars bind to proteins and warp their structure, turning functional proteins into dysfunctional Advanced Glycation Endproducts (AGEs). But this effect has only been shown to happen in test tubes: it’s not really clear that the same thing would happen in a living person, and in fact there’s good reason to believe that it won’t.

Instead, it appears that Carnosine may attack the same problem from a different angle, actually boosting the cell’s ability to clear out damaged proteins once they’re formed. One of the problems with damaged proteins is that their mangled structures often don’t give easy access to the enzymes that normally digest worn-out cellular components, making it difficult for the cell to remove them. Experimental studies have found that Carnosine reacts with proteins which have already been damaged by glycation and other assaults on their structural/functional integrity, forming “carnosylated” complexes which appear to be more easily removed than the original, warped protein.

At the same time, other such studies suggest that Carnosine revs up the proteasome – the cell’s “recycling center” for malformed proteins. Instead of blocking the formation of AGEs, in other words, Carnosine might actually help the body to eliminate glycated and other dysfunctional proteins.

The results at the cellular level are enticing. The question that begs to be answered next is: how do these effects translate out on a larger scale – on the health of our tissues and organs – when you supplement with Carnosine?

Cataracts & Macular Degeneration

Misshapen proteins accumulate across the entire structure of the eye with “normal” aging, interfering with visual functioning. AGEs, in particular, play a major role in the universal age-related loss of eye structure and function, as well as in the more specific degenerative diseases of the aging eye, such as cataracts, glaucoma, and age-related macular degeneration (AMD).

Delivering Carnosine directly to the eye itself, then, would be predicted to be the ideal real-world test case for the test-tube finding that Carnosine can protect against – and perhaps even actually undo – the damage wrought by glycation and other protein-warping mechanisms of aging. New human trials have shown that topical Carnosine delivers on this promise.

 

Research

Tired Eyes & Clearer Vision

In an open study protocol, scientists gave Carnosine supplements to patients in late middle age who had varying degrees of visual impairment, but no symptomatic cataracts. Over the course of two to six months, the scientists observed that the use of topical Carnosine supplementation “appears to alleviate eye tiredness and … obviously improve eyesight, giving more clear vision.” Users found that topical Carnosine “could brighten and relax their eyes.” The improvements were statistically significant.

Cataracts

In an open investigation, 96 senior citizens who had suffered with senile cataracts for as little as two to as much as twenty-one years applied topical Carnosine supplements to their eyes three or four times a day, for periods ranging from three to six months. At the end of the study, the researchers found that Carnosine eye drops lead to improvements in eyesight and lens transparency in the great majority of patients. They saw improvements in every single one of the people suffering with early-stage cataracts; and even in mature senile cataract, a remarkable 80% of the topical Carnosine users experienced a benefit. The investigators went on to expand on these preliminary results with the sequential treatment of nearly a thousand cataract patients – to similar success and with no side effects observed.

Reduced Haze After Laser Surgery

21 people, with a total of 27 affected eyes, who had suffered corneal haze following Photorefractive Keratectomy (PRK – a form of laser surgery) (27 eyes were affected), were given topical Carnosine three times a day for two months. Fully 57.9% of people using the Carnosine eye drops experienced a reduction in corneal haze intensity, accompanied by an improvement in visual acuity; only 14% of users’ eyes continued to worsen. The positive results appeared in patients with low to moderate myopia, who had developed moderate haze (1 to 1.5 on a 3-point scale) within a month of surgery; there are no known treatments which are effective for late corneal haze of a higher grade than this.

In a second, larger, and more rigorous trial, patients who had just undergone PRK (41 patients (including 73 affected eyes)) or LASIK (“LAser in-Situ Keratomileusis” – 34 people, 60 eyes) were given the same thrice-daily regimen of topical Carnosine as was used in the first trial, while corresponding control groups (41 PRK patients and 34 LASIK recipients) received Carnosine-free dummy eye drops. Compared with people applying the placebo solution, the healing of the corneal epithelium of people supplementing with Carnosine eye drops took 35 hours less time to regrow – a speeding of the epithelial re-growth process of nearly a day and a half. Even better, users of topical Carnosine supplements following LASIK were one-third less likely to suffer corneal haze than those using the un-supplemented eye drops!

Corneal Disorders

In clinical studies involving 109 patients, these scientists found Carnosine effective in cases of primary and secondary corneal dystrophy, corneal erosions, trophic keratitis, and bullous keratopathy, as well as corneal ulcerations and other damage wrought on the cornea by viral and bacterial infections. The Russian government accordingly approved topical Carnosine supplementation for these uses as early as 1997.

New & Improved: N-Acetyl-Carnosine over Carnosine

Instead of using Carnosine itself, more recent trials have used N-acetyl-L-carnosine, a metabolite of Carnosine, which the body slowly converts back into free Carnosine, allowing for slower, more thorough delivery of free Carnosine into the eye’s tissues and access to areas of the eye where Carnosine itself cannot penetrate.

Cataracts: In a randomized, double-blind, placebo-controlled study, scientists first evaluated the baseline state of cataract victims’ eyes. The scientists then randomly handed out either topical N-Acetyl-L-Carnosine supplements (as a 1% solution) or an identical-looking placebo solution. A third group of cataract patients received no eye drops at all. After just six months, ninety percent of the eyes of people supplementing with N-Acetyl-L-Carnosine eye drops saw their visual acuity improve, with the strength of the effect ranging from a modest gain to a full 100% recovery. In the same period, only 5.7 percent of the eyes of people using the stand-in eye drops were judged to have improved visual acuity, while over a third (34.7%) suffered a worsening of acuity, and most (60%) simply retained the same impaired vision with which they had begun the study. In a two-year extension, N-Acetyl-L-Carnosine eye drop users were shown to maintain their improved vision, while the eyesight of those not receiving the supplement continues to deteriorate.

Glare sensitivity: On top of the gains in visual acuity, researchers observed that N-Acetyl-L-Carnosine topical supplementation also clearly improves glare sensitivity, with 88.9% of N-Acetyl-L-Carnosine eye drop users’ eyes seeing improvements ranging from 27 to 100% after just six months; again, the divide separating supplementers from non-supplementers was unequivocal, with over half (56.3%) of nonusers’ eyes deteriorating and none getting any better. The glare sensitivity tests were not repeated at the two-year mark.

At the end of the full two-year trial, the image analyses showed that 47.8% of the lenses of N-Acetyl-L-Carnosine topical supplement users were clearer than they were at the beginning of the trial – and none had worsened. Meanwhile, none of the people whose eye drops did not contain N-acetyl-L-carnosine showed improvements on the image analysis, while a predictable 47.4% of the lenses continuing the hazy slide into blindness.

Night Driving

Another randomized, placebo-controlled study tested the effects of N-Acetyl-L-Carnosine on glare disability in drivers. Glare disability is excessive luminance or a problematic distribution of luminance which disturbs vision. Elderly drivers often experience this problem at night from oncoming headlights. The problem increases with age, and is one of the first complaints of drivers with initial cataracts. Drivers aged 65-69 years have the second highest fatality rate per mile traveled (exceeded only by the youngest drivers), even though they travel fewer miles per year. In this study, N-Acetyl-L-Carnosine eye drops were given to 65 older drivers with a cataract in at least one eye, and to 72 adult drivers with no cataracts for 4 months. Eyes treated with N-Acetyl-L-Carnosine had a statistically significant improvement in visual acuity and glare sensitivity compared to the control group. N-Acetyl-L-Carnosine improved the drivers’ vision whether or not they had cataracts, but the improvements were especially noticeable in those with cataracts.

Proven Results

For the first time, a simple topical treatment was proven to actually reverse the clouding of the cataracted lens – and the treatment was not a drug, but a natural substance naturally present in healthy cells.

Good for Healthy Eyes Too

The results of the many human trials constitute proof-of-concept for the wider concept that the use of topical Carnosine – and especially the unique Carnosine metabolite N-Acetyl-L-Carnosine, a biological “delivery system” for Carnosine – can help the eyes to heal from damage, and allow the body to remove dysfunctional proteins from the eye. When you put that together with the fact that malformed proteins are implicated in nearly every aspect of age-related visual decline, these studies clearly point to the potential of Carnosine/N-Acetyl-L-Carnosine eye drops to support the maintenance of normal, healthy eye structure and function in people whose eyes are just fine – and whose owners want to keep them that way.

An Important Note About Formulation: Only Use What the Studies Used

In all of the clinical trials, N-Acetyl-L-Carnosine has been used by itself, with no added antioxidants or other ingredients other than formulants (such as buffering agents) required to make a viable N-Acetyl-L-Carnosine ophthalmic solution. The metabolism of N-Acetyl-L-Carnosine into Carnosine depends on enzymes in the body (N-acetylesterase and N-acetyltransferase), which accomplish this transformation as part of their normal biological function. The activity of these enzymes can be significantly changed by the presence of antioxidants other than N-Acetyl-L-Carnosine in the area.

Therefore, mixing N-Acetyl-L-Carnosine with other antioxidants – such as vitamin A or alpha-tocopherol – in the same topical solution is asking for trouble. Under these circumstances, the conversion of N-Acetyl-L-Carnosine into Carnosine will be altered, with unpredictable results on the levels of free Carnosine delivered to different tissues within the eye.

The results observed in clinical trials flow from the natural, unmodified kinetics of these enzymes. Products which adulterate N-Acetyl-L-Carnosine with unnecessary additional antioxidants are untested, potentially ineffective, and may theoretically even damage your vision in the long term by leading to the inappropriate tissue-specific release of Carnosine, conversion to histamine, and resultant chronic, low-level inflammation. Ensure that any N-Acetyl-L-Carnosine supplement you use is free of extraneous antioxidants.

 

Market Trends

Eye problems such as glaucoma, cataracts and macular degeneration are a common concern as aging occurs. Most medical treatments intended for these conditions include the use of medications and surgical corrective measures. Some common supplements for eye health include lutein, vitamin A, beta-carotene, bilberry and other flavonoids.

AOR Advantage

If you are looking for a single product to protect or improve your eye health and vision, Ortho•Eyes seems to do it all! Since N-acetyl-L-carnosine helps reduce the build-up of aging proteins in the eyes, it can potentially help with any eye condition related to aging, and the clinical studies have shown positive results for many of them. The most common comment from Ortho•Eyes users is that is brightens the eyes and reduces visual strain.

References

Babizhayev MA. Rejuvenation of Visual Functions in Older Adult Drivers and Drivers with Cataract During a Short-Term Administration of N-Acetylcarnosine Lubricant Eye Drops. Rejuvenation Research. 2004;7(3):186-198.

Babizhayev MA, Deyev AI, Yermakova VN, Semiletov YA, Davydova NG, Kurysheva NI, Zhukotskii AV, Goldman IM. N-Acetylcarnosine, a natural histidine-containing dipeptide, as a potent ophthalmic drug in treatment of human cataracts. Peptides. 2001 Jun; 22(6): 979-94.

Kourenkov VV, Cheloudtchenko VM, Sergienko VI, Formazyuk VE, Beuerman RW, Maitchouk DY. Beta-alanyl-L-histidine (Carnosine) in the management of the healing process during and after excimer laser refractive surgery. Invest Ophthalmol Vis Sci. 1999 Mar 15; 40(4): 584(Abs544).

Maichuk IuF, Formaziuk VE, Sergienko VI. Development of carnosine eye drops and assessing their efficacy in corneal diseases. Vestn Oftalmol. 1997 Nov-Dec; 113(6): 27-31.

Wang AM, Ma C, Xie ZH, Shen F. Use of carnosine as a natural anti-senescence drug for human beings. Biochemistry (Mosc). 2000 Jul; 65(7): 869-71.

 

Abstract

N-acetylcarnosine lubricant eyedrops possess all-in-one universal antioxidant protective effects of L-carnosine in aqueous and lipid membrane environments, aldehyde scavenging, and transglycation activities inherent to cataracts: a clinical study of the new vision-saving drug N-acetylcarnosine eyedrop therapy in a database population of over 50,500 patients.

Am J Ther. 2009 Nov-Dec;16(6):517-33.

Babizhayev MA, Micans P, Guiotto A, Kasus-Jacobi A.

The antioxidant activity of L-carnosine (beta-alanyl-L-histidine, bioactivated in ocular tissues) versus N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine, ocular-targeted small dipeptide molecules) was studied in aqueous solution and in a lipid environment, employing liposomes as a model of lipid membranes. Reactive oxygen species (ROS) were generated by an iron/ascorbate promoter system for induction of lipid peroxidation (LPO). L-carnosine, which is stabilized from enzymatic hydrolysis, operates as a universal aldehyde and ROS scavenger in both aqueous and lipid environments and is effective at preventing ROS-induced damage to biomolecules. Second-generation carnosine analogs bearing the histidyl-hydrazide moiety were synthesized and tested versus L-carnosine for their ability to reverse the glycation process, also known as the Maillard reaction, and reverse the stable intermolecular cross-links, monitored in the glucose-ethylamine Schiff base model, ultimately resulting in the formation of the advanced glycation end products (AGEs) from nonenzymatic glycation, accumulating in numerous body tissues and fluids. The obtained data demonstrate the transglycation properties of the ophthalmically stabilized L-carnosine and L-carnosine histidyl-hydrazide derivatives tested and can be used to decrease or predict the occurrence of long-term complications of AGE formation and improve therapeutically the quality of vision and length of life for diabetes mellitus patients and survivors with early aging. Scientists at Innovative Vision Products, Inc. (IVP), developed lubricant eyedrops designed as a sustained-release 1% N-acetylcarnosine prodrug of L-carnosine. The eyedrops contain a mucoadhesive cellulose-based compound combined with corneal absorption promoters and glycerine in a drug-delivery system. Anti-aging therapeutics with the ophthalmic drug eyedrop formula including N-acetylcarnosine showed efficacy in the nonsurgical treatment of age-related cataracts for enrolled participants in the prospective, randomized, double-masked, placebo-controlled crossover clinical trial after controlling for age, gender, and daily activities. In a cohort in excess of 50,500 various patients seeking cutting-edge medical care, the N-acetylcarnosine topical eyedrops target therapy was demonstrated to have significant efficacy, safety, and good tolerability for the prevention and treatment of visual impairment in this older population with relatively stable patterns of causes for blindness and visual impairment. Overall, accumulated study data demonstrate that the IVP-designed new vision-saving drugs, including N-acetylcarnosine eyedrops, promote health vision and prevent vision disability from senile cataracts, primary open-angle glaucoma, age-related macular degeneration, diabetic retinopathy, and aging. N-acetylcarnosine eyedrop therapy is the crown jewel of the anti-aging medical movement and revolutionizes early detection, treatment, and rejuvenation of aging-related eye-disabling disorders. N-acetylcarnosine, as an innovative medical science tool and component of the home medicine and alternative medicine approaches, has the potential to alleviate visual impairment and its associated social, economic, and political woes for an aging population.

 

Rejuvenation of Visual Functions in Older Adult Drivers and Drivers with Cataract During a Short-Term Administration of N-Acetylcarnosine Lubricant Eye Drops.

Rejuvenation Research. 2004;7(3):186-198.

Babizhayev MA.

The purpose of this study was to examine using the original halometer glare test of the type of visual impairment mediated by the increased glare sensitivity (halos) and associated with poorer visual function in both the better and worse eyes of older adult drivers and older drivers with cataract. The clinically validated (by Innovative Vision Products Inc.) formula of 1% N-acetylcarnosine (NAC) lubricant eye drops were applied topically to the eyes of older drivers to reduce glare disability and improve distance acuities for driving. This was a randomized, double-blind, placebo-controlled study. The examined subjects consisted of 65 older adults with cataract in one or both eyes, and 72 adult drivers who did not have cataract in either eye. In the control group, comparison with baseline values showed some variability of data in gradual worsening of glare sensitivity at red and green targets and minimal VA changes over 4 months. In the NAC-treated group, 4-month follow-up generally showed an improvement in VA and a significant improvement in glare sensitivity at red and green targets was documented in worse and better eyes using a critical cut point halometer score for driving. The NAC-treated eyes had statistically significant difference in VA, glare sensitivity compared with the control group (p  0.001) at 4-month timepoint of treatment, as supported by the overall t-test results of the ratio of the follow-up data to the baseline values. Tolerability of NAC eyedrops was good in almost all patients, with no reports of ocular or systemic adverse effects. It would be advisable for traffic safety if a Halometer glare sensitivity test was implemented for vehicles and/or was regularly added to the requirements for a driver’s licence. The results of this study provide a substantial basis for further evaluation of NAC in the treatment and prevention of vision impairment in the older population of drivers for legal driving. The developed ophthalmic drug NAC formula showed potential for the non-surgical treatment of age-related cataracts.

 

N-Acetylcarnosine, a natural histidine-containing dipeptide, as a potent ophthalmic drug in treatment of human cataracts.

Peptides. 2001 Jun; 22(6): 979-94.

Babizhayev MA, Deyev AI, Yermakova VN, Semiletov YA, Davydova NG, Kurysheva NI, Zhukotskii AV, Goldman IM.

A study was designed to document and quantify the changes in lens clarity over 6 and 24 months in 2 groups of 49 volunteers (76 eyes) with an average age of 65.3 /- 7.0 enrolled at the time of diagnosis of senile cataracts of minimal to advanced opacification. The patients received N-acetylcarnosine, 1% sol (NAC) (26 patients, 41 eyes = Group II), placebo composition (13 patients, 21 eyes) topically (two drops, twice daily) to the conjunctival sac, or were untreated (10 patients, 14 eyes); the placebo and untreated groups were combined into the control (reference) Group I. Patients were evaluated upon entry, at 2-month (Trial 1) and 6-month (Trial 2)-intervals for best corrected visual acuity (b/c VA), by ophthalmoscopy and the original techniques of glare test (for Trial 1), stereocinematographic slit-image and retro-illumination photography with subsequent scanning of the lens. The computerized interactive digital analysis of obtained images displayed the light scattering/absorbing centers of the lens into 2-D and 3-D scales. The intra-reader reproducibility of measuring techniques for cataractous changes was good, with the overall average of correlation coefficients for the image analytical data 0.830 and the glare test readings 0.998. Compared with the baseline examination, over 6 months 41.5% of the eyes treated with NAC presented a significant improvement of the gross transmissivity degree of lenses computed from the images, 90.0% of the eyes showed a gradual improvement in b/c VA to 7-100% and 88.9% of the eyes ranged a 27-100% improvement in glare sensitivity. Topographic studies demonstrated less density and corresponding areas of opacification in posterior subcapsular and cortical morphological regions of the lens consistent with VA up to 0.3. The total study period over 24 months revealed that the beneficial effect of NAC is sustainable. No cases resulted in a worsening of VA and image analytical readings of lenses in the NAC-treated group of patients. In most of the patients drug tolerance was good. Group I of patients demonstrated the variability in the densitometric readings of the lens cloudings, negative advance in glare sensitivity over 6 months and gradual deterioration of VA and gross transmissivity of lenses over 24 months compared with the baseline and 6-month follow-up examinations. Statistical analysis revealed the significant differences over 6 and 24 months in cumulative positive changes of overall characteristics of cataracts in the NAC-treated Group II from the control Group I. The N-acetylated form of natural dipeptide L-carnosine appears to be suitable and physiologically acceptable for nonsurgical treatment for senile cataracts.

 

Use of carnosine as a natural anti-senescence drug for human beings.

Biochemistry (Mosc). 2000 Jul; 65(7): 869-71.

Wang AM, Ma C, Xie ZH, Shen F.

Carnosine is an endogenous free-radical scavenger. The latest research has indicated that apart from the function of protecting cells from oxidation-induced stress damage, carnosine appears to be able to extend the lifespan of cultured cells, rejuvenate senescent cells, inhibit the toxic effects of amyloid peptide (A beta), malondialdehyde, and hypochlorite to cells, inhibit glycosylation of proteins and protein-DNA and protein-protein cross-linking, and maintain cellular homeostasis. Also, carnosine seems to delay the impairment of eyesight with aging, effectively preventing and treating senile cataract and other age-related diseases. Therefore, carnosine may be applied to human being as a drug against aging.

 

Beta-alanyl-L-histidine (carnosine) in the management of the healing process during and after excimer laser refractive surgery.

Invest Ophthalmol Vis Sci. 1999 Mar 15; 40(4): 584(Abs544).

Kourenkov VV, Cheloudtchenko VM, Sergienko VI, Formazyuk VE, Beuerman RW, Maitchouk DY.

Purpose: To determine the role of beta-alanyl-L-histidine in improving the healing process and decreasing the potential of the haze development after photorefractive keratectomy (PRK) and LASIK.

Methods: Animal experimental study: 42 rabbits (84 eyes) received PRK. Treated group (44 eyes) received beta-alanyl-L-histidine eye drops 3 times a day during first 3 days after surgery. Control group (40 eyes) received placebo. Clinical study: 41 patients (73 eyes) received 5% carnosine eye drops 3 times a day during first 4 days after PRK in addition to the routine medications. The control group (41 patients) received usual routine medications after PRK. Corneas of 34 patients undergoing LASIK (60 eyes) were irrigated with 5% carnosine eye drops after the corneal flap was lifted. In the control group (60 eyes) BSS was used for irrigation.

Results: Animal experimental study: In treated group full reepithelization occurred 18 /- 4(p=0.02) hours earlier than in control group. Post surgical haze was observed only in 4 eyes in the treated group versus 7 in the control group. After 4 weeks haze disappeared in all cases. Clinical study: In treated group full reepithelization occurred 35 /-7 (p=0.01) hours earlier in comparison with the control group. Among the patients with LASIK in the group irrigated with 5% carnosine post surgical haze was found in 6% of cases, versus 9% in control group. In all cases, except one in the control group, haze disappeared after 6 months.

Conclusions: Beta-alanyl-L-histidine and related dipeptides have been shown to protect cell membranes from oxidative damage. This ability and their antineoplastic and immunomodulating effects are proposed to stimulate reepithelization after PRK and decrease number of cases with corneal post surgical haze after LASIK.

 

Development of carnosine eyedrops and assessing their efficacy in corneal diseases.

Vestn Oftalmol. 1997 Nov-Dec; 113(6): 27-31.

Maichuk IuF, Formaziuk VE, Sergienko VI.

Stable eye drops of 5% carnosine have been developed. Trials of the drug on mice, rats, rabbits, and dogs showed it to be well tolerated at both total and local levels. In animals the eye drops did not affect the diameter of the pupil, nor did they increase the intraocular pressure. Clinical trials were carried out in 109 patients. Carnosine eye drops exerted a good therapeutic effect in corneal erosion, trophic keratitis, postherpetic epitheliopathy, primary and secondary corneal dystrophy, and bullous keratopathy. Used in combined treatment, the eye drops accelerated healing of corneal ulcers in herpesvirus and bacterial infection or dry keratoconjunctivitis. The Pharmacological Committee of the Ministry of Health and Medical Industry of the Russian Federation permitted 5% carnosine eye drops for medical use.

 

N alpha-acetylcarnosine is a prodrug of L-carnosine in ophthalmic application as antioxidant.

Clin Chim Acta. 1996 Oct 15;254(1):1-21.

Babizhayev MA, Yermakova VN, Sakina NL, Evstigneeva RP, Rozhkova EA, Zheltukhina GA.

The naturally occurring compound N alpha-acetylcarnosine (NAC) is proposed as the prodrug of L-carnosine (C) resistant to enzymatic hydrolysis by human serum carnosinase. Rabbit eyes were treated with 1% NAC, C or placebo and extracts of the aqueous humor from the anterior eye chamber were analyzed for imidazole content by reverse phase analytical high performance liquid chromatography (HPLC), thin-layer (TLC) and ion-exchange chromatographic techniques. The topical administration of pure C to the rabbit eye did not lead to accumulation of this compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eye. NAC showed dose-dependent hydrolysis in its passage from the cornea to the aqueous humor, releasing C after 15. 30 min of ocular administration of prodrug in a series of therapeutical modalities: instillation < or = subconjunctival injection < or = ultrasound induced phoresis. Different treatment techniques showed excellent toleration of 1% NAC by the eye. Once in the aqueous humor, C might act as an antioxidant and enter the lens tissue when present at effective concentrations (5-15 mmol/l). The advantage of the ophthalmic prodrug NAC and its bioactivated principle C as universal antioxidants relates to their ability to give efficient protection against oxidative stress both in the lipid phase of biological membranes and in an aqueous environment. NAC is proposed to treat ocular disorders which have the component of oxidative stress in their genesis (cataracts, glaucoma, retinal degeneration, corneal disorders, ocular inflammation, complications of diabetes mellitus, systemic diseases).

 

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