Intraocular Administration Research Articles

Drug delivery for intracerebral of flunarizine hydrochloride after intraocular administration in rats.

Intraocular administration was a commonly route of administration in clinic, but most of the intraocular administration was only used to treat local ocular diseases. Based on the particularity of the ocular structure, this article mainly explored the feasibility of flunarizine hydrochloride in the treatment of ischemic cerebral vascular diseases (ICVD) by intraocular administration. A total of 150 SD rats were randomly divided into 3 groups with intraocular, intragastric, and intravenous administration, respectively. The doses were 14 mg/kg for intraocular and intragastric groups and 5 mg/kg for intravenous group. The plasma and brain concentration of flunarizine hydrochloride were analyzed by high performance liquid chromatography (HPLC). Main pharmacokinetic parameters and absolute bioavailability were evaluated. Brain targeting of flunarizine hydrochloride through intraocular administration was studied by drug targeting index of brain (DTIbrain). Maximum contentration (Cmax) and area under the time-concentration curve from o to t (AUC0-t) of plasma after intraocular administration were significantly higher than those of plasma after intragastric administration (both P<0.05). Cmax and AUC0-t of brain after intraocular administration were significantly higher than those of brain after intragastric administration (both P<0.05). The bioavailability of plasma and brain after intraocular administration was 18.67% and 34.67%, respectively, which was higher than 14.32% and 21.56% of plasma and brain after intragastric administration. The DTIbrain of intraocular administration was 1.84, and the DTIbrain of intragastric administration was 1.48. Flunarizine hydrochloride could be absorbed into the systemic circulation after intraocular administration. Not only the absolute bioavailability but also the brain targeting index of intraocular administration is higher than that of intragastric administration.

Comparative Pharmacokinetics of Nimodipine in Rat Plasma and Tissues Following Intraocular, Intragastric, and Intravenous Administration

We investigated the pharmacokinetics of nimodipine (NMD) in rats plasma and tissues following intraocular (io), intragastric (ig), and intravenous (iv) administration at doses of 5.0mg/kg io and iv and 10.0mg/kg ig. After a single dose of NMD, plasma, heart, liver, spleen, lung, kidney, and brain samples were collected at the scheduled time points. The concentration of NMD in rat plasma and tissues was determined by high-performance liquid chromatography, and the main pharmacokinetic parameters were calculated and compared. NMD was rapidly absorbed and reached the maximum plasma concentration in approximately 5min after io administration. The absolute bioavailability after io administration was higher than that after ig administration (40.05% vs. 5.67%). There were significant differences in the tissue distribution of NMD with different administration routes. After io administration, NMD was distributed more in the lung, spleen, and brain tissues, and less in the kidney. The maximum drug concentration after io administration in the heart, liver, spleen, lung, kidney, and brain was 1.00, 0.47, 2.02, 1.47, 0.22, and 5.79 times higher than that after via ig administration, and the area under the curve value was 0.59, 0.78, 1.71, 1.84, 0.25, and 4.59 times greater, respectively. Nimodipine appears to achieve systemic effects via io administration. Compared with ig, io administration could significantly increase NMD distribution in the brain tissue, indicating that NMD could be delivered to the brain via io administration.

Retinal and Optic Nerve Integrity Following Monocular Inactivation for the Treatment of Amblyopia.

In animal models, monocular deprivation (MD) by lid closure mimics the effects of unilateral amblyopia in humans. Temporary inactivation of one or both eyes with intraocular administration of tetrodotoxin (TTX) has recently been shown to promote recovery from the anatomical effects of MD at post-critical period ages when standard recovery strategies fail. In the current study, the retinae and optic nerves of animals subjected to 10 days of monocular retinal inactivation were assessed for pathological changes as a means of assessing the viability of this potential new amblyopia therapy. Retinal sections from both eyes were subjected to hematoxylin and eosin staining and were then examined for cell density and soma size in the ganglion cell layer (GCL). Sections of the optic nerve from each eye were examined for neurofilament protein, myelin, glial cell density, and glial fibrillary acidic protein (GFAP). Our study revealed no evidence of gross histopathological abnormalities following inactivation for 10 days, nor was there evidence of degeneration of axons or loss of myelin in the optic nerve serving inactivated eyes. On all measurements, the inactivated eye was indistinguishable from the fellow eye, and both were comparable to normal controls. We confirmed that our inactivation protocol obliterated visually-evoked potentials for 10 consecutive days, but visual responses were restored to normal after the effects of inactivation wore off. Notwithstanding the critical need for further assessment of ocular and retinal health following inactivation, these results provide evidence that retinal inactivation as a treatment for amblyopia does not produce significant retinal damage or degeneration.

Humoral immunity provided by a novel infectious bronchitis vaccine supplemented by bacterium-like particles (BLPs)

Infectious bronchitis (IB) is a notable disease of poultry flocks that results in economic loss. As a consequence of the presence of various IB virus (IBV) serotypes, control strategies, such as vaccination, should be replaced by provide broad protective immunity against the disease to date. Gram-positive enhancer matrix particles, or so-called bacterium like particles (BLPs), obtained from the bacterium Lactococcus lactis (L. lactis), have demonstrated an adjuvancy effect by providing demanding mucosal and humoral immune responses, as well as a protective cellular immunity whenever delivered admixed with a vaccine via intranasal or intraocular administration. In this study, for the first time, attempts were made to investigate the impact of an IBV vaccine supplemented by various doses of BLPs on induced levels of humoral immunity against IB. For this purpose, increasing doses of derived BLPs (0, 0.15, 0.3, and 0.6 mg dry weight per bird) were admixed with IBV live attenuated H120 serotype vaccine, and were delivered via ocular administration to 4 equal groups of 10 specific pathogen-free (SPF) chickens in 4 groups: control, BLP1, BLP2, and BLP3, respectively. In addition, 10 SPF chickens that were not immunized comprised the Unvaccinated group. Blood was collected from 5 members of each group weekly for 35 days. Levels of IgG antibodies in the sera were then assayed using ELISA. Weight gain and the feed conversion ratio of each group were also recorded weekly. Finally, 3 birds from each group were necropsied to evaluate probable lesions. The best results were obtained in the BLP1 group, with IBV vaccination at a low dose of admixed BLPs boosted immediate anti-IBV humoral responses; however, the results were not significantly different from those of the Control group, but were still feasible enough for application in the field. In conclusion, BLPs could be a desirable adjuvant for IBV vaccines to increase immunity in chickens.

Микроимпульсная циклофотокоагуляция в комбинированном лечении неоваскулярной глаукомы

Introduction. Neovascular glaucoma (NVG) is one of the most prognostically unfavorable forms of the glaucomatous process. The leading pathogenetic mechanism for the development of NVH is hypoxia of the inner layers of the retina, leading to the development of endothelial vascular growth factors (VEGF), which induce neovascular proliferation. In the presence of newly formed vessels in the corner of the anterior chamber, the use of traditional surgical methods for treating glaucoma is limited. That is why the search for a new pathogenetically oriented methods for the treatment of NVH is still acute issue in ophthalmology. Purpose. To evaluate the preliminary results of combined treatment, including intraocular introduction of anti-VEGF therapies (ranibizumab) and micropulse cyclophotocoagulation, in patients with secondary neovascular glaucoma. Materials and methods. The study included 15 patients (15 eyes) with secondary neovascular glaucoma. The value of intraocular pressure (IOP) before surgery ranged from 28 to 44 mm Hg. (average 36.3 ± 4.4 mm Hg), the number of hypotensive drops was 3.5 ± 0.5. The combine treat of patients including the intraocular administration of a VEGF inhibitor (ranibizumab) and through 7-14 days transscleral diode-laser cyclophotocoagulation in micropulse mode on the device «Cyclo G6 Glaucoma Laser System» (IRIDEX, USA) with a laser power of 2000 mW, an exposition of 160 s (80 s in each hemisphere) and a duty cycle of 31.3%. Results. All treatment procedures were performed without complications. By 6 months of follow-up, the average IOP level was 26.9 ± 3.3 mm Hg, the number of hypotensive drops was reduced to 2.7 ± 0.7 drugs. By 1 month of observation, a decrease in the number of newly formed vessels of the iris was achived in all patients. According to ultrasound biomicroscopy, the thickness of the ciliary body (CT) before treatment was on average 0.58 ± 0.14 mm. By 6 months of follow-up, no cases of postoperative atrophy of CT was diagnosed, the thickness of the CT was on average 0.53 ± 0.11 mm. According to the data of optical coherence tomography in the angiography mode, in all cases there was a positive dynamic in 1 month after combined treatment - a significant decrease in macular edema, the area of the retinal nonperfusion zone and the number of newly formed vessels. Conclusion. Combined treatment of patients with secondary neovascular glaucoma, including intraocular introduction of anti-VEGF therapies and micropulse cyclophotocoagulation, is an effective and safe method for reducing IOP.

A novel flunarizine hydrochloride-loaded organogel for intraocular drug delivery in situ: Design, physicochemical characteristics and inspection.

We developed a safe and efficacious drug delivery system for treatment of brain diseases. A novel in-situ gel system was prepared using soybean oil, stearic acid and N-methyl-2-pyrrolidinone (NMP) (10:1:3, v/w/v). This system had low viscosity as a sol in vitro and turned into a solid or semi-solid gel in situ after administration. The poorly water-soluble drug flunarizine hydrochloride (FNZ) was incorporated into this "organogel" system. Organogel-FNZ was characterized by light microscopy, differential scanning calorimetry (DSC) and rheology. Drug release in vitro was investigated. The initial "burst" effect did not occur in organogel-FNZ, which is different from other gels formed in situ. Pharmacokinetic studies were undertaken in rats using gel administration (14mgkg-1), intravenous administration (5mgkg-1) and administration using drops (14mgkg-1). Organogel-FNZ could reduce the clearance rate and prolong the duration of action, in the plasma and brain tissues of rats. The peak serum concentration, area under the curve and absolute bioavailability of the organogel-FNZ group were higher than those of the intraocular- drops group. Organogel-FNZ is a promising drug-delivery system for treatment of brain diseases by intraocular administration.

Assessment of effective dose preparability of bevacizumab for intraocular administration

Assessment of effective dose preparability of bevacizumab for intraocular administration

Intravitreal injection of peptides PnPa11 and PnPa13, derivatives of Phoneutria nigriventer spider venom, prevents retinal damage.

Background: PnPa11 and PnPa13 are synthetic peptides derived from Phoneutria nigriventer spider venom, which display antinociceptive and neuroprotective properties. In this work, we evaluated the safety of intravitreal use and the neuroprotective effect of these peptides.Methods: The cytotoxicity and the antiangiogenic activity of these peptides were evaluated by the sulforhodamine-B method and chicken chorioallantoic membrane (CAM) assay, respectively. The in vivo safety was analyzed in Wistar rats that were intravitreally injected with different doses (0.50; 1.25; 2.50; 3.75 and 5.00 µg/mL) of these peptides (right eye, n = 6). The retinal function was assessed by electroretinography exams (ERG), intraocular pressure (IOP), and histological analyzes. In order to investigate the neuroprotective effect, Wistar rats received intravitreal injections (right eye, n = 6) of peptides at 1.25 µg/mL and then were exposed to blue LED light. In addition, the visual function and the retinal microstructure were verified.Results: Cytotoxicity analyses demonstrated that the peptides did not present any toxicity over ARPE-19 (adult retinal pigmented epithelial) cell line and the antiangiogenic study highlighted that the peptides promoted the reduction of blood vessels. The intravitreal injection did not cause major changes, neither induced any irreversible damage. In the retinal degeneration assay, the ERG records demonstrated that the prior treatment with PnPa11 and PnPa13 protected the retina from damage. Morphological analyses confirmed the ERG findings. Immunoblotting analyses revealed that PnPa11 increased Erk1/2, NR2A, and NR2B retinal expression after the light stress model, but did not cause Akt1 activation, while PnPa13 prevented Erk1/2 and Akt1 dephosphorylation.Conclusions: The intraocular administration of these peptides was well tolerated and presented protective activity against retinal degeneration, suggesting the potential use of these peptides as neuroprotectors in the ophthalmological field.

Intravitreal anti-VEGF agents and cardiovascular risk.

Antagonists of Vascular Endothelial Growth Factor (Anti-VEGF) are widely administered by intravitreal injection for the treatment of ocular pathologies such as Age-related Macular Degeneration, Diabetic Macular Edema, Proliferative Diabetic Retinopathy and occlusion of retinal vessels. Anti-VEGF agents, in particular bevacizumab, were introduced in oncology to inhibit tumor-induced angiogenesis feeding neoplastic tissues. Subsequently, other specific agents were developed for intraocular administration. Whereas systemic administration of anti-VEGF agents in oncology is burdened by increased risk of arterial hypertension and embolism, agents administered for ophthalmic indications are delivered locally into the eye globe in much smaller quantities. Nevertheless, clinical observations have raised the possibility that, even in these conditions, anti-VEGF agents may increase cardiovascular risk in patients who, being elderly and/or diabetic, are intrinsically prone to such events. This paper aims at reviewing the current knowledge on VEGF and its pharmacologic antagonists from mechanistic and side effect points of view, with specific reference to patients with sight-threatening conditions. Internists should be aware of the need to collaborate with ophthalmologists and pharmacovigilance operators to define as best as possible the risk/benefit balance of intravitreal agents in patients who might lose their sight if left untreated, or increase their risk of suffering a cardiovascular event if treated.

The ying and yang of idebenone: Not too little, not too much – cell death in NQO1 deficient cells and the mouse retina

Idebenone has recently been investigated as a drug therapy for Leber's hereditary optic neuropathy (LHON), a rare genetic mitochondrial disease that causes rapid and progressive bilateral vision loss. Although several studies have shown that idebenone can promote vision recovery in patients with LHON, the evidence for the efficacy of idebenone is still limited. Idebenone failed to demonstrate superiority over placebo in the primary end-points of the only published randomised, double-blind, placebo-controlled trial. There appears to be a patient-specific response to idebenone with high variability in therapeutic outcomes. A recent study suggested that the cytosolic enzyme NAD(P)H: quinone acceptor oxidoreductase (NQO1) is the major enzyme involved in the activation of idebenone, and the beneficial effects of idebenone are dependent on the expression of NQO1. Here, we confirm the NQO1-dependent activity of idebenone, but we also show, for the first time, that the cytotoxicity of idebenone is linked to cellular expression of NQO1. Upon idebenone administration, cells deficient in NQO1 show a marked decrease in viability in comparison to NQO1 expressing cells, with idebenone causing ROS production and deleterious effects on ATP levels and cell viability. In addition, our data highlights that only cells expressing NQO1 can significantly activate idebenone, indicating that other proposed metabolic activation pathways, such as complex II and glycerol-3-phosphate dehydrogenase, do not play a significant role in idebenone activation. Furthermore, we provide evidence of idebenone-induced toxicity in the retina ex-vivo, which can be explained by the variation of NQO1 expression between different cell types in the mouse retina. Idebenone mediated cell rescue in the rotenone ex vivo model also indicated that this drug has a narrow therapeutic window. These findings will help to guide the development of future therapies and drug delivery strategies including intra-ocular administration. The specific dependence of idebenone activity on NQO1 may also explain the variation in patient outcomes in clinical trials.

Effect of different doses of borneol on the pharmacokinetics of vinpocetine in rat plasma and brain after intraocular administration

The effect of different doses of borneol on the pharmacokinetics of vinpocetine after intraocular administration in the rat plasma and the brain was investigated.Intraocular administration of vinpocetine (3 mg/kg) was performed, in combination with different doses (0, 5, 10, and 20 mg/kg) of borneol. Intravenous administration of vinpocetine was used as a control (1 mg/kg). The concentrations of vinpocetine in the rat plasma and the brain were determined using a liquid chromatography-tandem mass spectrometry (LC–MS/MS) method. Using the non-compartmental models with the DSA 2.0 software, the main pharmacokinetics parameters and the brain-targeting effect evaluated.In comparison with intravenous administration, after intraocular administration of vinpocetine alone, the absolute bioavailability (F) of vinpocetine was 43.82% for the plasma, and the drug target index (DTI) was 1.05 for the brain. After intraocular administration of vinpocetine combined with different doses of borneol, the relative bioavailability (Fr) of vinpocetine in the plasma was increased by 130.46–182.90%. The relative bioavailability (Fr) of vinpocetine in the brain was improved (147.19–225.36%). The DTI was 1.12, 1.18, and 1.21 for 5, 10, and 20 mg/kg of borneol, respectively.Compared with the intraocular administration of vinpocetine alone, the co-administration of different doses of borneol resulted in an obvious brain targeting effect.

Has retinal gene therapy come of age? From bench to bedside and back to bench.

Retinal gene therapy has advanced considerably in the past three decades. Initial efforts have been devoted to comprehensively explore and optimize the transduction abilities of gene delivery vectors, define the appropriate intraocular administration routes and obtain evidence of efficacy in animal models of inherited retinal diseases (IRDs). Successful translation in clinical trials of the initial promising proof-of-concept studies led to the important milestone of the first approved product for retinal gene therapy in both US and Europe. The unprecedented clinical development observed during the last decade in the field is however highlighting new challenges that will need to be overcome to bring gene therapy to fruition to a larger patient population within and beyond the realm of IRDs.

Ocular Biodistribution Studies using Molecular Imaging.

Classical methodologies used in ocular pharmacokinetics studies have difficulties to obtain information about topical and intraocular distribution and clearance of drugs and formulations. This is associated with multiple factors related to ophthalmic physiology, as well as the complexity and invasiveness intrinsic to the sampling. Molecular imaging is a new diagnostic discipline for in vivo imaging, which is emerging and spreading rapidly. Recent developments in molecular imaging techniques, such as positron emission tomography (PET), single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), allow obtaining reliable pharmacokinetic data, which can be translated into improving the permanence of the ophthalmic drugs in its action site, leading to dosage optimisation. They can be used to study either topical or intraocular administration. With these techniques it is possible to obtain real-time visualisation, localisation, characterisation and quantification of the compounds after their administration, all in a reliable, safe and non-invasive way. None of these novel techniques presents simultaneously high sensitivity and specificity, but it is possible to study biological procedures with the information provided when the techniques are combined. With the results obtained, it is possible to assume that molecular imaging techniques are postulated as a resource with great potential for the research and development of new drugs and ophthalmic delivery systems.

Eyelid xanthelasma and its management

The article presents an overview of modern methods of treatment of eyelid xanthelasm: systemic treatment, local treatment-peeling with trichloroacetic acid, cryotherapy, intraocular administration of pingiangmycin, laser removal, radiowave removal on the Surgitron device with a frequency of 4 MHz, as well as a guide to choosing the appropriate method.

Pharmacokinetics of Nimodipine after Intraocular Administration in Rats

Objective To explore the pharmacokinetics of nimodipine in plasma of rats after intraocular administration.Methods Totally 135 SD rats were randomly divided into three groups according to drug administration routes:intraocular(io group),intravenous (iv group),and intragastric (ig group). The doses were 5.0 mg/kg for IO and IV groups and 10.0 mg/kg for IG group. The serum nimodipine level was analyzed by high performance liquid chromatography. The main pharmacokinetic parameters were calculated and compared.Results The pharmacokinetic parameters in io group were as follows:Cmax:0.52 mg/ml;tmax:5.0 min;and AUC0-t:21.10 mg/(ml·min). The main pharmacokinetic parameters in iv group were as follows:Cmax:3.62 mg/ml;and AUC0-t:52.58 mg/(ml·min). The main pharmacokinetic parameters in ig group were as follows:Cmax:0.20 mg/ml;tmax:5.0 min;and AUC0-t:5.98 mg/(ml·min).Conclusions Nimodipine is rapidly absorbed after io administration,and the ophthalmic formulation has a higher bioavailability than the oral solution. Therefore,the io route may help to improve the treatment effectiveness of cardiovascular diseases.

Intraocular administration of tetramethylpyrazine hydrochloride to rats: a direct delivery pathway for brain targeting?

The purpose of this study was to compare the pharmacokinetic profile of tetramethylpyrazine hydrochloride (TMPH) in rat plasma and tissues following intravenous (iv), intragastric (ig) and intraocular (io) administration. After io, ig and iv administration of a single dose at 10 mg/kg, tissue and plasma samples drawn from the femoral artery were collected at timed intervals. The concentration of TMPH in the samples was analyzed using high-performance liquid chromatography (HPLC). The area under the concentration–time curve (AUC) and the drug targeting efficiency percentage (DTE(%)) were calculated to evaluate the targeting efficiency of the drug with the three different administration routes. After io administration, TMPH was rapidly absorbed to reach its peak plasma and brain concentration within 5 min. The systemic bioavailability obtained with io administration was greater than that obtained through the ig route (63.22% vs. 16.88%). The AUCt rank order of the iv administration group was AUCkidney >AUCheart >AUCliver >AUCbrain >AUCspleen >AUClung; that of the ig administration group as AUCkidney >AUCliver >AUCheart >AUCspleen >AUCbrain >AUClung; while that of the io administration group was AUCkidney >AUCbrain >AUCheart >AUCliver >AUCspleen >AUClung. The ratio of the AUCbrain value between the io route and iv injection was 1.05, which was greater than that obtained after ig administration (0.30). The DTE after io administration was calculated: brain (165.72%), heart (97.76%), liver (113.06%), spleen (105.31%), lung (163.40%) and kidney (135.31%). The io administration group showed obvious drug transport to the brain. These results indicate that TMPH is rapidly absorbed from the eye into the systemic circulation, and there may be a direct translocation pathway for TMPH from the eye to the brain. Therefore, io administration of TMPH could be a promising alternative to intravenous and oral approaches.

Variations of immunoglobulin A in serum, tracheal, and intestinal tissues in chickens following inoculation of two strains of Newcastle disease vaccines

To elucidate secretory immunoglobulin A (IgA) response as a part of mucosal immunity, it is decided to compare the effectiveness of intraocular administration of Hitchner B1 and thermostable I-2 vaccines in broiler chickens challenged with viscerotropic velogenic Newcastle disease virus (vvNDV) (Herts33). For this purpose, 301-day-old chicks were randomly divided in to the four groups. Groups 1 and 2 were inoculated with I-2 and HB1 vaccines twice via intraocular route with 1-week intervals, and groups 3 and 4 were considered positive and negative controls and birds were challenged 2 weeks after the second inoculation. Protection rate in I-2 and HB1 vaccine groups was 100% and 97% respectively with no significant differences (P > 0.05). All vaccinated groups showed elevation in ND HI antibody titer after vaccination. There were no significant differences (P > 0.05) in ND HI antibody between two vaccinated groups. First levels of detectable total IgA in a serum sample were observed 3 dpv1. No significant differences (P > 0.05) were observed between two vaccinated groups in IgA antibody titer in sera. The vaccinated groups were evaluated by IHC for detection IgA in the trachea and intestine. There were some differences between the vaccinated groups but these differences were not significant. Experimental studies have shown that both vaccines induce antibody production in mucosal surface and circulatory system and thermostable I-2 vaccine could be successfully used in the broiler chicken as effective as HB1 vaccine, so I-2 vaccine could be a suitable heat resistance candidate to reduce mortality in the poultry industry faced to vvND.

Useful properties of siRNA-coated gold nanoparticles as a mini-nanocarrier platform for intraocular administration

Wet type age-related macular degeneration results in the reduction and loss of eyesight and is closely correlated with angiogenesis. Small interfering siRNA (siRNA) is a functional nucleic acid used as a knockdown tool to control target gene expression in a sequence-dependent manner. In contrast, siRNA can potently inhibit angiogenesis in an “independent” manner via its interaction with Toll-like receptor 3. In this study, siRNA was conjugated with ultra-small gold nanoparticles to prevent the distribution of siRNA outside the eye, and the usefulness of this mini-carrier with siRNA against angiogenesis was investigated. Thiolated siRNA (siRNA-hexaethyleneglycol-SH) was conjugated to the surface of gold nanoparticles through a coordinate bond. The nanoparticles were small (approximately 10 nm in diameter) and carried approximately 7.6 siRNA molecules oriented vertically. These nanoparticles suppressed luciferase gene expression in a cell line stably expressing luciferase. The siRNA-gold nanoparticles inhibited tube formation by human endothelial cells on Matrigel efficiently. These siRNA-gold nanoparticles may be useful for treating angiogenesis resulting from age-related macular degeneration.

Involvement of ciliary neurotrophic factor in early diabetic retinal neuropathy in streptozotocin-induced diabetic rats

ObjectiveCiliary neurotrophic factor (CNTF) has been evaluated as a candidate therapeutic agent for diabetes and its neural complications. However, its role in diabetic retinopathy has not been fully elucidated.MethodsThis is a randomized unblinded animal experiment. Wistar rats with streptozocin (STZ)-induced diabetes were regularly injected with CNTF or vehicle control in their vitreous bodies beginning at 2 weeks after STZ injection. A total of five injections were used. In diabetic rats, the levels of CNTF and neurotrophin-3 (NT-3) were evaluated by enzyme-linked immunosorbent assays (ELISA) and real-time PCR. The abundance of tyrosine hydroxylase (TH) and β-III tubulin was detected by western blot. Transferase-mediated dUTP nick-end labeling staining (TUNEL) was used to detect cell apoptosis in the retinal tissue. The activation of caspase-3 was also measured.ResultsThe protein and mRNA levels of CNTF in diabetic rat retinas were reduced compared to control rats. In addition, retinal ganglion cells (RGCs) and dopaminergic amacrine cells appeared to undergo degeneration in diabetic rat retinas, as revealed by transferase-mediated dUTP nick-end labeling staining (TUNEL). Tyrosine hydroxylase (TH) and β-III tubulin protein levels also decreased significantly. Intraocular administration of CNTF rescued RGCs and dopaminergic amacrine cells from neurodegeneration and counteracted the downregulation of β-III tubulin and TH expression, thus demonstrating its therapeutic potential.ConclusionOur study suggests that early diabetic retinal neuropathy involves the reduced expression of CNTF and can be ameliorated by an exogenous supply of this neurotrophin.

INVASIVE METHODS OF TREATMENT OF VITILIGO

The review of the literature is devoted to the use of various invasive treatments for a disease such as vitiligo. The article deals with the majority of methods of treating dermatosis with damage to the integrity of the skin from intraocular administration of corticosteroid preparations, immunomodulators to various methods of “surgical” intervention. Also, examples of techniques of micronidling and nidling with tacrolimus in combination with UVB are given. In addition, some data from one of the potentially effective methods in the treatment of this pathology-the use of platelet-enriched plasma are presented.