Morphological Changes in the Retina Under Conditions of Experimental In Vivo Regional Ischemia/Reperfusion.

Two models of retinal ischemia/reperfusion were developed in an experiment on rats and structural changes in eye tissues in the early and late postischemic periods were studied. Ischemia/reperfusion was modeled by elevation of intraocular pressure to 110 mm Hg for 30 min with air injection into the anterior chamber of the eye with a special device or subconjunctival administration of 0.2 ml 4×10-6 M endothelin-1. Morphological studies of the retina of enucleated eyes were performed in 3, 7, and 30 days after ischemia/reperfusion. In 3 days, signs of retinal ischemia were seen (retinal edema and ganglion cell damage). In the late post-ischemic period (30 days), atrophy of the outer nuclear and outer plexiform layer of the retina was observed in animals with retinal ischemia/reperfusion caused by intraocular pressure elevation and complete destruction of neuronal cells was found after administration of endothelin-1.

[Assessing resveratrol effect on ocular blood flow in experiment].

AIM: To study the effect of resveratrol on ocular blood flow in vivo in healthy rats and those that underwent retinal ischemia/reperfusion. MATERIAL AND METHODS: The experimental study was performed on 40 Wistar rats (40 eyes). For ocular blood flow evaluation, color Doppler imaging (CDI), power Doppler (PD), and pulsed-wave spectral Doppler ultrasonography were performed using the Voluson E8 Expert ultrasonic diagnostic system (GE Healthcare). All rats were given resveratrol per os for 2 months of the study. Retinal ischemia/reperfusion injury was induced by a subconjunctival injection of endothelin-1. The control group included 10 intact animals. RESULTS: Signs of ischemic damage of the anterior and posterior eye segments were less pronounced in rats that were given resveratrol during both pre-ischemic (30 days) and post-ischemic (30 days) periods of follow-up. There was also a statistically significant increase in the peak systolic and end diastolic velocity of blood flow as well as a decrease in the resistive index of retrobulbar arteries in those rats that underwent ischemia/reperfusion as compared to the controls. CONCLUSION: Long-term resveratrol use (2 months) has proved effective in improving ocular blood flow in a rat model of retinal ischemia/reperfusion injury.

Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 4. Age-related eye disease. SkQ1 returns vision to blind animals.

Mitochondria-targeted cationic plastoquinone derivative SkQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) has been investigated as a potential tool for treating a number of ROS-related ocular diseases. In OXYS rats suffering from a ROS-induced progeria, very small amounts of SkQ1 (50 nmol/kg per day) added to food were found to prevent development of age-induced cataract and retinopathies of the eye, lipid peroxidation and protein carbonylation in skeletal muscles, as well as a decrease in bone mineralization. Instillation of drops of 250 nM SkQ1 reversed cataract and retinopathies in 3-12-month-old (but not in 24-month-old) OXYS rats. In rabbits, experimental uveitis and glaucoma were induced by immunization with arrestin and injections of hydroxypropyl methyl cellulose to the eye anterior sector, respectively. Uveitis was found to be prevented or reversed by instillation of 250 nM SkQ1 drops (four drops per day). Development of glaucoma was retarded by drops of 5 microM SkQ1 (one drop daily). SkQ1 was tested in veterinarian practice. A totally of 271 animals (dogs, cats, and horses) suffering from retinopathies, uveitis, conjunctivitis, and cornea diseases were treated with drops of 250 nM SkQ1. In 242 cases, positive therapeutic effect was obvious. Among animals suffering from retinopathies, 89 were blind. In 67 cases, vision returned after SkQ1 treatment. In ex vivo studies of cultivated posterior retina sector, it was found that 20 nM SkQ1 strongly decreased macrophagal transformation of the retinal pigmented epithelial cells, an effect which might explain some of the above SkQ1 activities. It is concluded that low concentrations of SkQ1 are promising in treating retinopathies, cataract, uveitis, glaucoma, and some other ocular diseases.

[Therapy of stromal herpetic keratitis with a new immunomodulator likopide]. / Novyí immunomoduliator likopid (GMDP) v lechenii gerpeticheskikh stromal'nykh keratitov.

Likopide (N-acetylglucosamine-(beta 1-4)-N-acetylmuramyl-alanyl-D-isoglutamine) is a synthetic analog of muramylpeptides, characterized by immunomodulating properties and increasing the nonspecific resistance to infections. Seventy patients with ophthalmic herpes were examined, 35 of these were treated with likopide and 35 were administered placebo. Fifty-two of these suffered from stromal keratitis with ulceration and 18 had no ulcers. The trials were carried out by the double blind test with placebo. Likopide was administered orally in 10 mg tablets twice daily according to the following protocol: 3 days of treatment, 3-day interval, and 3-day treatment. All the patients were administered local specific (acyclovir ointment) and general symptomatic therapy. Immunological studies were carried out before and after therapy. Clinical assessment showed a reliably high therapeutic efficacy of likopide, its total value (excellent and good results) being as high as 88.5%. The mean duration of therapy with likopide was 11.4 +/- 0.4 days versus 15.2 +/- 0.9 days in the placebo group. Judging by the recovery criteria (arrest of inflammation, epithelization of the cornea, resorption of corneal infiltration and edema, resorption of iritis) likopide reliably accelerated healing and ensured a higher increase of vision acuity. Likopide reliably decreased the rate of detection of herpes simplex virus antigen in the involved eye conjunctiva in comparison with the placebo group patients (97.1% of negative cases versus 60%). The drug was well tolerated by the patients, no side effects were observed. Skin allergic tests with likopide showed no drug allergies.

[Isolation of purified and concentrated human interferon from Namalwa cells]. / Poluchenie ochishchennogo i kontsentrirovannogo chelovecheskogo interferona iz kletok liniii Namal'va.

The interferon produced in the cultured Namalwa cells was purified and concentrated according to the method of K. Cantell and S. Hirvonen developed for purification of leukocyte interferon. A preparation concentrated 500-fold had the antiviral activity of 10(6) IU/ml at a specific activity of 1-3 X 10(6) per 1 mg of protein. The amount of protein in the preparation was approximately 0.6 mg/ml, that of cell DNA less than 100 ng/ml. The experiments demonstrated that the virus inducer of interferon and possible contaminant viruses were removed on purification. The preparation had no oncogenic potency on inoculation of newborn Syrian hamsters, was harmless by intraperitoneal inoculation of mice and on multiple inoculations on rabbit eye cornea, was not toxic in cell cultures.

[Main proteolytic inhibitors in ocular herpes]. / Osnovnye ingibitory prpoteoliza pri oftal'mogerpese.

Alterations in content of main inhibitors of proteolysis alpha 1-antitrypsin and alpha 2-macroglobulin as well as activity of neutral proteases in blood serum were studied in herpetic impairment of human and rabbit retina. Unspecific protective reaction of the blood proteolytic inhibitors developed in ophthalmoherpes. In the acute period of the disease content of alpha 1-antitrypsin was increased and the content of alpha 2-macroglobulin was decreased. Slow development of the disease was observed when the content of alpha 1-antitrypsin was decreased at the period of acute inflammation. Estimation of proteolytic inhibitors might serve as an useful test for characteristics and prognosis of herpetic keratitis.

[Pharmacokinetics and antiviral activity of riodoksol in an ointment and in ophthalmic drug films in ocular herpes]. / Farmakokinetika i protivovirusnaia aktivnost' riodoksol v mazi i glaznykh lekarstvennykh plenkakh pri oftal'mogerpese.

A study was made on the pharmacokinetics in rabbit eye tissues of a new antiviral drug riodoksol in the form of ointment and biosoluble eye films. The pharmacokinetics of the drug was studied in eye tissues of normal rabbits and in those infected with herpes simplex virus. It was disclosed that four-fold application of 0.25% ointment produced the therapeutic concentration of the drug only in the cornea. Application of eye films made it possible to attain the therapeutic concentrations of riodoksol in the cornea and, within the first 3 hours, in the iris and humor of the anterior chamber. No differences were found in the drug concentrations in the tissues of intact and infected animals. Appraisal of the therapeutic efficacy of riodoksol regimens devised in experimental surface herpetic keratitis of rabbits has shown an adequacy of a single administration of eye films containing 0.5 mg of the substance and four-fold application of 0.25% ointment.