Healthy Albino Rabbits Research Articles

Measurement of vitreous humor pressure in vivo using an optic fiber pressure sensor

We conducted a study to assess the pressure difference between the aqueous and vitreous humors in rabbit eyes using a direct intraocular pressure (IOP) measurement method. A micro-optic-fiber pressure sensor was utilized for this purpose. Preliminary experiments with enucleated porcine eyes confirmed the sensor's accuracy in measuring both aqueous and vitreous humor pressure. The main study involved six healthy albino rabbits, where the sensor measured the pressure in the anterior chamber (aIOP) and posterior vitreous-cavity (pIOP). These measurements were compared to aIOP values obtained through rebound tonometry. Additionally, pre- and postoperative pressure comparisons were made after performing a vitrectomy. Results revealed a significant disparity between aqueous and vitreous humor pressures. Prior to vitrectomy, pIOP was 22.8 mmHg, over twice as high as aIOP (11.0 mmHg), but decreased to a similar level following the procedure. Comparison between the sensor measurements and rebound tonometry showed agreement in aIOP values. In conclusion, our study demonstrates that vitreous humor pressure is consistently higher than aqueous humor pressure, reaching the upper limit of normal IOP. Furthermore, vitrectomy effectively reduces pIOP, aligning it with aIOP. These findings contribute valuable insights into intraocular pressure dynamics and have implications for clinical interventions targeting ocular pressure regulation.

AN EXPERIMENTAL STUDY PERFORMED TO COMPARE THE HEPATOPROTECTIVE ACTIVITY OF ALOE VERA AND SILYMARIN IN CARBON TETRA CHLORIDE (CCL4)-INDUCED HEPATOTOXICITY IN ALBINO RABBITS

Objective: The aim of the study was to compare the hepatoprotective activity of Aloe vera and Silymarin in carbon tetrachloride (CCl4)-induced hepatotoxicity in albino rabbits. Methods: The study was conducted on 18 healthy albino rabbits of either sex weighing 1.5–2.0 kg, divided into three groups. Hepatotoxicity was induced in rabbits by administering CCl4(0.05 mg/kg) intraperitoneally. Alcoholic extracts of leaves of A. vera and Silymarin were administered orally for 20 days from day 1 to day 20 in the doses of 100mg/kg/day with the help of a syringe in groups II and III respectively. Results: Group I: There was an increase in the level of serum transaminase (p<0.001), serum alkaline phosphatase (p<0.001), serum bilirubin (p<0.001), and a decrease in serum albumin (p<0.001) due to hepatotoxic effect of CCl4 when compared to day 0 of the same group. Group II: A. vera extract was found to reduce the level of aspartate transaminase (p<0.0001), alanine transaminase (p<0.0001), serum alkaline phosphatase (p<0.0001), serum bilirubin (p<0.0001), and increase in serum albumin (p<0.0001). Group III: Silymarin was found to reduce the level of aspartate transaminase (p<0.0001), alanine transaminase (p<0.0001), serum alkaline phosphatase (p<0.0001), serum bilirubin (p<0.0001), and increase in serum albumin (p<0.0001). The findings of Group II and Group III were found to be statistically highly significant when compared with Group I. On histopathology, Group II showed maximum reduction in fatty changes compared to Group III. Conclusions: A. vera extract and Silymarin both showed a decline in hepatotoxic effects induced by CCl4. Comparatively, A. vera exhibited higher protection in restoration of liver function and regeneration of liver cells than Silymarin.

Olanzapine Mesoporous Nanostructured Lipid Carrier: Optimization, Characterization, In Vivo Assessment, and Physiologically Based Pharmacokinetic Modeling.

A promising approach has been emerging to enhance dissolution of hydrophobicdrugsby encapsulation in mesoporous silica materials. Olanzapine is a practically insoluble antipsychotic drug which is subjected to excessive first pass effect and shows inadequate oral bioavailability. Therefore, mesoporous silica was used to improve bioavailability of olanzapine incorporated in nano-structured lipid carriers (NLCs). These systems were characterized for their particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE) and differential scanning calorimetry (DSC) as well asits release profile. The optimized mesoporous NLC system displayed nano-spherical particles (120.56 nm), possessed high entrapment efficiency (88.46%) and the highest percentage of drug released after six hours (75.13%). The biological performance of the optimized system was assessed in comparison with the drug suspension in healthy albino rabbits. The optimized system showed significantly (P < 0.05) prolonged MRT (8.47 h), higher Cmax (22.12± 0.40 ng/ml) and Tmax (2.0 h) values compared to drug suspension. Physiologically based pharmacokinetic (PBPK) model was simulated and verified. All the predicted results were within 0.6 and 1-fold of the reported data. To set a conclusion, in vitro results as well as in vivo pharmacokinetic study and PBPK data showed an enhancement in bioavailability of the optimized NLCs system over the plain drug suspension. These results proved the potentiality of incorporating olanzapine in mesoporous NLC for a significant improvement in oral bioavailability of olanzapine.

Optimization of Glipizide Floating Matrix Tablet Using Simplex Lattice Design

The aim of the present study was to prepare the floating matrix tablet of glipizide by applying Simplex lattice design using kappa carrageenan, Hydroxypropylmethylcellulose K15M and sodium bicarbonate as independent variable. The similarity factor (f2), time to release 50 % of drug and time to release 90 % of drug were taken as dependent factors. A total of 14 batches were prepared as given by Design-Expert® Software (version- 9.0.6, Stat-Ease) and the response obtained for the dependent variables was statistically evaluated. Radiological study was performed on healthy albino rabbits for checking the gastroretention for optimized floating tablet of glipizide. The results indicated that the formulation G-simplex lattice design 8 with 50 mg of Hydroxypropylmethylcellulose, 30 mg of kappa carrageenan and 10 mg of sodium alginate is the optimized formulation with highest desirability. The in vivo X-ray imaging study clearly revealed that the optimized formulations remained afloat in gastric fluid up to 12 h in the stomach of rabbit, which shows the possibility of the formulation to remain in the stomach of human being for the desired period. It was concluded that the simplex lattice design is suitable for efficiently optimizing the floating matrix tablet of glipizide.

FORMULATION DEVELOPMENT AND IN VIVO EVALUATION OF PIOGLITAZONE INCLUSION COMPLEXES: A FACTORIAL STUDY

Objective: The objective of the study was to evaluate the individual main effects and combined (or interaction) effects of cyclodextrin (β cyclodextrin), surfactant (Poloxamer 407) and polyvinylpyrrolidone K30 (PVP K30) on the solubility and dissolution rate of pioglitazone in a series of 23 factorial experiments. The inclusion complexes were evaluated for pharmacokinetics and in vivo performance in comparison to pioglitazone pure drug.Methods: Among the various approaches complexation with cyclodextrins has gained good acceptance in recent years in the industry for enhancing the solubility and dissolution rate of poorly soluble drugs. As per the phase solubility studies, a 23 factorial study was used to prepare the solid inclusion complexes and evaluated for the interactions and in vitro drug release. The best combinations were selected for in vivo performance in healthy albino rabbits. From the time versus plasma concentration data, various pharmacokinetic parameters such as peak concentration (Cmax), time at which peak occurred (Tmax), area under the curve (AUC), elimination rate constant (Kel), biological half-life (t1/2), percent absorbed to various times and absorption rate constant (Ka) were calculated in each case.Results: The solubility of pioglitazone in eight selected fluids containing β cyclodextrin (βCD), Poloxamer 407 and PVP K30 as per 23 factorial studies was determined. Combination of βCD with Poloxamer 407 and PVP K30 resulted in a much higher enhancement (13.85-7.06 folds) in the solubility of pioglitazone than the βCD alone. Solid inclusion complexes of pioglitazone-βCD were prepared with and without Poloxamer 407 and PVP K30 by kneading method as per 23- factorial design. Analysis of variance (ANOVA) indicated that the individual main effects of βCD, Poloxamer 407 and PVP K30 and their combined effects in enhancing the solubility and dissolution rate (K1) were highly significant (P&lt;0.01). The t1/2 value of pioglitazone estimated (6.92-7.46 h) in the present study was in good agreement with the literature reported value of 6-10 h. Pioglitazone was absorbed slowly when given orally with an absorption rate constant (Ka) of 0.629 h-1 and a peak plasma concentration (Cmax) of 11.40±0.7 µg/ml was observed at 4.0 h after administration. All the pharmacokinetic parameters namely Cmax, Tmax, Ka and (AUC)0∞ indicated rapid and higher absorption and bioavailability of pioglitazone when administered as βCD complexes. A 3.43 and 4.67 fold increase in the absorption rate (Ka) and a 1.49 and 1.67 fold increase in (AUC)0∞ was observed respectively with pioglitazone-βCD (1:2) and pioglitazone-βCD (1:2)-Poloxamer 407 (2%) complexes when compared to pioglitazone pure drug.Conclusion: Combination of βCD with Poloxamer 407 gave higher rates of absorption and bioavailability of pioglitazone than is possible with βCD alone. Hence the combination of βCD with Poloxamer 407 is recommended to enhance the absorption and bioavailability of pioglitazone, a BCS class II drug.

Pharmacological evaluation of &lt;i&gt;Vernonia elaeagnifolia&lt;/i&gt; (Asteraceae) leaves in hyperlipidemic albino rabbits

Purpose: To evaluate the antihyperlipidemic efficacy and phytochemical constituents of Vernonia elaeagnifolia aqueous leaf extract. Method: Qualitative phytochemical analysis of V. elaeagnifolia leaves was performed. Thirty healthy albino rabbits were divided into six groups (n = 6). Cholesterol powder (0.5 g/kg) in 10 mL coconut oil (vehicle) was given orally to induce hyperlipidemia. The aqueous leaf extract of Vernonia elaeagnifolia was administered at 250 mg/kg and 500 mg/kg per oral. Lipid profile, hepatic enzymes and oxidative stress markers were evaluated. Results: Phytochemical screening indicated the presence of tannins, proteins, flavonoids, phenols, alkaloids and saponins. Oral administration of cholesterol powder significantly (p < 0.05) raised the level of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and triglyceride (TG) along with significant (p < 0.05) decrease in serum concentration of high-density lipoprotein cholesterol (HDLc). Concentration of serum TC, LDL-c, TG and liver enzymes was significantly reduced in V. elaeagnifolia -treated groups. The levels of oxidative stress markers were restored to normal when the animals were treated with V. elaeagnifolia leaf extract; increased levels of antioxidant enzymes were observed. Conclusion: The aqueous leaf extract of V. elaeagnifolia possesses antihyperlipidemic and antioxidant potentials that are dose-dependent. However, further studies are required to develop the plant for therapeutic applications. Keywords: Hyperlipidemia, Oxidative stress markers, Cholesterol, Vernonia elaeagnifolia

Ocular hypotensive effects of a Rho-associated protein kinase inhibitor in rabbits.

PurposeRipasudil is a novel Rho-associated protein kinase inhibitor that is used to treat ocular hypertension. However, the comparison of the intraocular pressure (IOP)-lowering effects between ripasudil alone and other ocular hypotensive drugs has not been studied thoroughly. The purpose of this study is to examine the ocular hypotensive effects of 0.4% ripasudil, 2% pilocarpine, 0.5% timolol and 0.1% dorzolamide in rabbits. We also studied the IOP changes when 0.4% ripasudil was combined with 2% pilocarpine, 0.5% timolol or 0.1% dorzolamide.MethodsOne drop of saline solution, 0.4% ripasudil, 0.5% timolol, 2% pilocarpine or 1% dorzolamide or a combination of these agents was applied topically to the left eyes of eight healthy albino rabbits. Posttreatment changes in the IOP of albino rabbits were monitored using a rebound tonometer over a 5-h time course. Changes in IOP after application of saline served as the control. One-way analysis of variance and Dunnett’s post hoc tests were used for statistical analyses.ResultsAfter topical instillation, 0.4% ripasudil resulted in significant decreases in IOP at 0.5 and 1 h compared with the control group. Treatment with timolol, pilocarpine or dorzolamide had no significant effect on IOP. Treatment with timolol, pilocarpine or dorzolamide in combination with ripasudil resulted in significant reductions in IOP at 1 h. However, none of these agents enhanced the IOP-lowering effects of ripasudil.ConclusionRipasudil has stronger IOP-lowering effects than timolol, pilocarpine or dorzolamide hypotensive agents in our rabbit model. Addition of timolol, pilocarpine or dorzolamide did not enhance the IOP-lowering effects of ripasudil alone.

A study on the effect of atorvastatin on the pharmacokinetic and antidepressant activity of fluoxetine

Background: Polypharmacy is of wide concern in drug interaction. It is the leading cause of adverse drug reaction, and consequently, increasing the possibility of hospitalization and escalating the cost of care. The incidence of coexisting depression and hyperlipidemia in patients is generally managed by providing numerous drugs for a longer period of time. Aims and Objectives: This study was conducted to observe the effect of atorvastatin on pharmacokinetic parameters of fluoxetine in healthy albino rabbits and to find possible interactions of atorvastatin on the antidepressant activity of fluoxetine using animal screening test. Materials and Methods: Two drugs: Fluoxetine and atorvastatin used concurrently were selected. Healthy male albino rabbits were used to determine the effect of atorvastatin on fluoxetine addressing its pharmacokinetic parameters, whereas rats and mice were used to assess the antidepressant activity of fluoxetine. Two animal models were used to determine its antidepressant activity. Forced swim test (FST) and tail suspension test (TST) were employed in exploring antidepressant activity. High-performance liquid chromatography was used to estimate fluoxetine concentration. Results: The concentration of serum fluoxetine showed slight increment after the atorvastatin treatment for 7 days at 2nd, 4th, 8th, 16th, and 24th h. The pharmacokinetic parameters: Area under the curve, area under first-order moment curve, t1/2, and Cmax of fluoxetine varied after atorvastatin treatment for 1 week in healthy albino rabbits. ‘’Furthermore, atorvastatin treatment for a week revealed a reduction in immobility time in rats and mice as shown by the FST and TST respectively. Conclusion: The results revealed the possibility of drug-drug interaction between fluoxetine and atorvastatin.

Nephroprotective Effect of the Leaves of Aloe barbadensis (Aloe Vera) against Toxicity Induced by Diclofenac Sodium in Albino Rabbits.

The present study was designed to evaluate the nephroprotective effect of the leaves of Aloe barbadensis against toxicity induced by diclofenac sodium in albino rabbits. Thirty-six healthy albino rabbits were randomly divided into six groups each with six animals. Group 1 served as the untreated control, group 2 was treated only with diclofenac sodium, group 3 with the nephroprotective drug silymarin and groups 4, 5, and 6 were treated with different doses of Aloe barbadensis,ie 200 mg/kg, 400 mg/kg and 600 mg/kg, respectively after being treated with diclofenac sodium. Blood samples were collected after every five days up to fifteen days. Haematological and histopathological parameters were determined by using diagnostic kits. Results of haematological studies showed that use of the powder of Aloe barbadensis normalized the level of different factors eg, white blood cells (WBCs), red blood cells (RBCs), platelet count, packed cell volume (PCV), mean cell volume (MCV) and haemoglobin (Hb) values. Histopathological studies showed that Aloe barbadensis ameliorated pyknotic nuclei in the renal epithelial cells and reduced oxidative stress by increasing the level of catalase and decreasing malondialdehyde (MDA) level. These results have shown that Aloe barbadensis can normalize oxidative stress and can be used as an effective nephroprotective agent against drug-induced nephrotoxicity.

INTRA-SCLERAL PARATHALAMUS IMPLANT: EFFICACY AND SAFETY IN RABBIT EYES.

A variety of anti-glaucomatous shunt designs have been proposed so far. This study evaluates the feasibility of a novel shunt design, the intra-scleral parathalamus implant (IPI), in a rabbit eye model. Ten healthy albino rabbits were included. Measurements of the IOP, using TonoPenXL, as well as ocular rigidity (OR) and aqueous outflow facility (AO), using a previously described methodology, were performed in both eyes of each animal. Subsequently, the IPI was implanted at the left eye of all animals whereas the right eye served as control. Measurements of IOP were repeated at weekly intervals for 2 months postoperatively whereas measurements of OR and AO were repeated at the 1st and 2nd postoperative week. The IOP decreased significantly whereas the AO increased significantly postoperatively at the operated eyes. A significant postoperative decrease in OR was also recorded at the operated eyes. Respective differences at the fellow eyes were statistically not significant. Two animals developed postoperative complications and were excluded from follow-up. Results imply that the implantation of the IPI is feasible in rabbit eyes with significant favorable effects on the IOP, AO and OR.

Topotecan vitreous and plasma levels and retinal toxicity after transcorneal intravitreal delivery in healthy albino rabbits: Alternative retinoblastoma treatment

To determine intravitreal and plasma concentrations and retinal toxicity after transcorneal intravitreal injection of 1 μg and 2 μg of topotecan (Hycamtin). Twelve healthy albino rabbits were included in this in vivo experiment. Six anesthetized albino rabbits received a single transcorneal intravitreal injection of 1 μg (group A) or 2 μg (group B) of topotecan. Vitreous and blood samples were collected until 168 h. Left eyes were treated with the same volume of saline. Plasma and vitreous levels of topotecan were determined by high-performance liquid chromatography. Area under the plasma concentration time curve (AUC) was calculated using trapezoidal rule. Clinical evidence of toxicity was classified into four grades according to anatomical structures. Electroretinograms (ERGs) were recorded. Time to maximum concentration was observed up to 2 h after drug injection in group A whereas up to 1 h in group B. Low levels of topotecan were detected in plasma in both groups and in the vitreous humor of the contralateral eye in group B. Topotecan levels (mean vitreous AUC in group A 2.55 μg/mL.h and in group B 5.338 μg/mL.h) were detectable up to 6 h in both groups. We observed following structural changes in rabbit eyes: corneal vascularization, cataract, hemophthalmus, choroidal edema and focal retinal atrophy. Abnormal ERGs were obtained. Our findings proved that transcorneal intravitreal administration of 1 μg and 2 μg of topotecan results in potentially cytotoxic intraocular concentrations. More studies are needed to establish the safety of topotecan for retinoblastoma in children.

Topotecan vitreous levels and retinal toxicity after repeated transcorneal intravitreal administration in healthy albino rabbits: an alternative for advanced retinoblastoma chemotherapy

Topotecan vitreous levels and retinal toxicity after repeated transcorneal intravitreal administration in healthy albino rabbits: an alternative for advanced retinoblastoma chemotherapy

Studies on influence of process variables on performance of gliclazide mucoadhesive microcapsules

Microencapsulation is a unique technique of controlled drug delivery system and is of major importance for effective alteration of drug release required to produce a novel formulation with desired characteristics to overcome the disadvantages of the conventional therapeutic dosage forms. Microcapsules offer efficient absorption and enhanced bioavailability owing to their higher surface area, however, mucoadhesive microcapsules render more intimate contact with the mucus membrane thereby leading to increase in the gastro intestinal residence time. Gliclazide is an oral hypoglycemic second generation sulfonyl urea, which is useful for a long-term treatment of non-insulin dependent diabetes mellitus. In the present investigation, the gliclazide microcapsules are formulated to control the release rate and improve the absorption across gastrointestinal membrane by employing ionic gelation method.The effect of various process variables such as curing time, stirring speed, stirring time, volume and concentration of curing reagent on entrapment efficiency, and drug release rate was studied. The microcapsules were evaluated for drug content, encapsulation efficiency, in vitro drug release studies. The optimized formulation was selected based on the entrapment efficiency and drug release rate.The optimized formulation of gliclazide microcapsules were evaluated for rheological properties, moisture content, swelling index, erosion studies, wall thickness and in vitro wash off test. The microcapsules formulated with 2:1 coat:core ratio by using 150 ml of 0.1M Cacl2 solution as curing reagent, at a stirring speed of 400 rpm for 60 minutes and a curing period of 48 hrs were found to be the optimum formulation. The drug release followed zero order kinetics and was controlled by peppas mechanism. The pharmacodynamic activity of optimized gliclazide microcapsules was conducted by measuring blood glucose levels in healthy albino rabbits. The percentage glucose reduction was calculated and the data was treated statistically. The hypoglycemic activity was extended up to 10 hours in case of microcapsules.

Preparation, Relative Toxicity, Chemotherapeutic Activity, and Pharmacokinetics of Liposomal SJA-95: A New Polyene Macrolide Antibiotic

The research work was designed to compare the relative toxicity, chemotherapeutic activity, and pharmacokinetic parameters of liposomal incorporated SJA-95 with that of free SJA-95, with an objective to reduce toxicity and improve therapeutic activity in vivo. Liposomal-incorporated SJA-95 (Lip SJA-95), prepared using the proliposome method, was found to exhibit a higher LD50 value in mice, and the relative toxicity was about 2.5 times lower than that of the free drug. Lip SJA-95 treatment in experimental mice model of Candidiasis showed increased survival and reduced fungal loads in various organs. The pharmacokinetic profile of the free and liposomal drug was evaluated by administration of free and Lip SJA-95 intravenously to healthy albino rabbits in a crossover fashion. Lip SJA-95 showed an initial fall in plasma levels and longer half-life. The improved microbial clearance following treatment with Lip SJA-95 could be attributed partly to an increased tissue uptake, which was reflected in a marked increase in volume of distribution (Vd) and longer half-life (T1/2). The present results clearly indicated that Lip SJA-95 treatment led to prolonged survival time, effective microbiological clearance, and reduced toxicity in the mice model of Candidiasis.

Effects of intraocular irrigation with melphalan on rabbit retinas during vitrectomy

To investigate the toxic effects of perfusion of intravitreal melphalan during vitrectomy on the rabbit retina. We performed electoretinography (ERG) in 18 eyes of 18 healthy albino rabbits before and after intraocular melphalan perfusion at concentrations of 5-, 10-, and 20-microg/ml during pars plana vitrectomy. Fellow eyes that underwent vitrectomy without melphalan served as controls. The histopathologic retinal changes were observed in both eyes of two rabbits from each group. In the 5-microg/ml perfusion group, the ERGs and histology showed no substantial changes compared with control fellow eyes during 28 days postoperatively. In the 10- and 20-microg/ml groups, the mean a-wave amplitude decreased to 52% and 31% respectively of the fellow eye; the mean b-wave amplitude decreased to 52% and 19% respectively. However, the peak implicit time of the a- and b-waves did not significantly differ in the 10- and 20-microg/ml groups during 28 days postoperatively. Histologic sections showed necrosis of the inner nuclear layer and thinning of the outer nuclear layer in the 10-microg/ml group. Loss of the outer nuclear layer and the photoreceptor layer and necrosis of the inner nuclear layer were observed in the 20-microg/ml group. The intravitreal 5-microg/ml melphalan perfusion during vitrectomy appears to be nontoxic to the retina. This therapeutic modality might be a potential treatment for retinoblastoma with vitreous seeding.

Ocular pharmacokinetics and bioavailability of 0.2% ganciclovir in-situ gelling eye drops

To compared the pharmacokinetics and bioavailability of 0.2% ganciclovir (GCV) in-situ gelling eye drops (GCV-ISG) with common GCV eye drops (GCV-ED) in rabbits. Forty-eight healthy albino rabbits were randomly divided into 2 groups, each group included 24 rabbits and 3 rabbits (6 eyes) were used at each time points. Each eye received 50 microl of GCV-ISG in experimental group, and the same amount of GCV-ED was given in the other group as the control. The tears and aqueous humors were collected at 5, 10, 15, 30, 45, 60, 90 and 120 minutes following topical application of GCV-ISG and GCV-ED, respectively, and the corneas were immediately dissected after euthanized. The samples from 6 eyes (3 animals) were obtained at each designed time point. All samples were stored -60 degrees C and then were assayed by reversed phase high performance liquid chromatography (HPLC). An unpaired Student's t-test and 3p97 pharmacokinetics software were used as statistical analysis. The drug levels in tears corneas and aqueous were significantly higher for GCV-ISG group than GCV-ED group at 5, 10 minutes (P < 0.05) and 120 minutes (P < 0.01). The areas under the curve (AUC0-120) of the drug concentrations versus times in tears, corneas and aqueous humors for GCV-ISG group were 2.22, 5.47 and 3.40 times as high as GCV-ED group within designed duration, respectively. The peak concentrations of GCV in aqueous humors for GCV-ISG group and the GCV-ED group were 4.79 microg/ml and 0.96 microg/ml, respectively. The half-lives of GCV in aqueous humors and corneas for GCV-ISG group were 59 minutes and 223 minutes, and for GCV-ED group were 43 minutes and 87 minutes, respectively. The peak concentration of GCV in aqueous humor in GCV-ISG group was 4.99 times higher than that in GCV-ED group (P < 0.01). 0.2% ganciclovir in-situ gelling eye drops significantly increases the drug penetration into cornea and aqueous humor, and prolongs the residence time in cornea and aqueous humor. The results suggest that 0.2% ganciclovir in-situ gelling eye drops may enhance the ocular bioavailability of ganciclovir in rabbit eye.

The mechanism and change in the optic nerve head (ONH) circulation in rabbits after glucose loading

Purpose. To assess the influence of the blood glucose level on ocular capillary circulation, we induced clinically significant hyperglycemia (200–300 mg/dl) in rabbits and investigated the changes in the optic nerve head (ONH) circulation. Methods. Hyperglycemia was induced by injection of glucose (5.6 mmol/kg) into an auricular vein of healthy albino rabbits and changes in the ONH circulation were measured by the laser speckle method. In order to examine the role of nitric oxide (NO), glucose was administered after intravenous injection of an NO synthetase inhibitor (N G -nitro-L-arginine methyl ester, L-NAME, 1 mg/kg), then changes in the ONH circulation were measured. Results. The blood glucose level reached a peak at 30 min after glucose loading and returned to its initial level by 2 hours. ONH circulation showed a 60% increase compared with its initial level at 15 min after glucose loading and subsequently remained almost unchanged throughout the 2-hour observation period. There were no significant changes of the blood pressure, heart rate, or intraocular pressure. The glucose-induced increase of ONH circulation was completely inhibited by pretreatment with L-NAME. Cocnlusions. ONH circulation was increased by administration of glucose to healthy rabbits. A high blood glucose level seems to promote ocular capillary circulation and NO as well as insulin appear to have a role in this process.