Non-systemic delivery of topical brimonidine to the brain: a neuro-ocular tissue distribution study

To date, the risks of central nervous system (CNS) side effects of topically administered ophthalmic therapeutic agents are thought to be the consequence of systemic absorption of these drugs. This paper envisions the possibility of drug delivery to the CNS following ocular application through non-systemic routes. After single instillation of 50 microl of 3H-radiolabeled Alphagan solution (0.2%) in the cul de sac of the right eye, three male albino rabbits (2-2.5 kg) were sacrificed at each time point (5, 15, 30 and 60 min). Both sides (eyes) specimens of aqueous humor, cornea, iris, lens, vitreous, conjunctiva, sclera, ciliary body, choroid, retina, optic nerve, optic tract and olfactory bulb were weighed, and blood samples were measured, before combustion in tissue oxidizer and radioactive liquid scintillation counting. Significant 3H-brimonidine levels were found in right and left optic nerves and tracts with extremely low corresponding drug levels in blood. Uveal tract (ciliary body, iris and choroid tissues) brimonidine levels were relatively high in the treated eye, and the highest among contralateral eye tissues. Our data provide the first case of good CNS availability after ocular application of conventional ophthalmic therapeutic agent, through non-systemic routes. Similar neuro-ocular pharmacokinetic studies should be adopted as a routine ocular therapeutics evaluation study.     

Comparative study of phase II biotransformation in rabbit ocular tissues.

To assess the biotransformational capability of ocular tissues in the rabbit, representative phase II enzymes were assayed in five tissues from the eye, and in the liver, kidney, and intestine. Within the eye, the iris/ciliary body exhibited the highest glutathione S-transferase activity, whereas the cornea possessed the highest specific activities for N-acetyl-, sulfo-, and UDP-glucuronosyl-transferases. Cornea, iris/ciliary body, choroid, and retina exhibited significant activities of p-aminobenzoic acid N-acetyltransferase, 2-naphthol sulfotransferase, and 1-chloro-2,4-dinitrobenzene glutathione S-transferase. Despite its size and protein content, lens displayed little or no biotransformational activity. Only the iris/ciliary body conjugated sulfobromophthalein with glutathione. UDP-glucuronsyltransferase activity varied depending on tested substrates and tissues. When compared to liver, kidney, or intestine, N-acetyltransferase activity in the iris/ciliary body nearly matched the rate measured in kidney, glutathione S-transferase activity in cornea and iris/ciliary body was nearly 70 and 89%, respectively, of the rate in intestine, and corneal sulfotransferase activity was greater than that in kidney. These data suggest that biotransformation pathways are present in the eye, and particularly in ocular tissues having adequate blood supply or interfacing with the external environment.     

Distribution of brimonidine into anterior and posterior tissues of monkey, rabbit, and rat eyes.

The objectives of the study were to evaluate the distribution of brimonidine (alpha2-adrenergic agonist) into anterior and posterior ocular tissues. Single or multiple doses of a 0.2 or 0.5% brimonidine tartrate solution were administered to one or both eyes of monkeys or to one eye of rabbits. Brimonidine was administered intraperitoneally to rats. After topical administration, [14C]brimonidine was rapidly absorbed into the cornea and conjunctiva and distributed throughout the eye. [14C]Radioactivity was higher and cleared more slowly in pigmented tissues (iris/ciliary body, choroid/retina, and optic nerve) than in nonpigmented tissues. Single and multiple dosing led to a similar drug distribution, with higher levels of brimonidine measured in pigmented tissues after multiple dosing. Most of the radioactivity extracted from ocular tissues represented unchanged brimonidine. In the rabbits and the monkey treated in only one eye, levels of radioactivity in the untreated eye were low, consistent with the low systemic levels and rapid drug clearance. Posterior ocular tissue concentrations of radioactivity exceeded systemic blood concentrations. The vitreous humor brimonidine concentrations in monkeys treated topically with 0.2% brimonidine tartrate was 82 +/- 45 nM. Vitreous levels in rabbits confirmed the penetration of brimonidine to the posterior segment. Similar concentrations of brimonidine (22 to 390 nM) were measured in the vitreous and retina of rats injected intraperitoneally with brimonidine. Both topically applied and systemically administered brimonidine reach the back of the eye at nanomolar concentrations sufficient to activate alpha2-adrenergic receptors. The brimonidine levels achieved at the retina are relevant for neuroprotection models.     

Dexamethasone distribution characteristic following controllable continuous sub-tenon drug delivery in rabbit

Drug delivery systems are required to be safe, minimally invasive and effectively delivery drug to the target tissues. But delivery drugs to the eye has not yet satisfied this need. Here, we focused on examining the distribution of dexamethasone (DEX) in ocular and plasmic samples following controllable continuous sub-Tenon drug delivery (CCSDD) of dexamethasone disodium phosphate (DEXP) in rabbit, and to compare that with two traditional routes: subconjunctival injection and intravenous injection. The DEX concentration was analyzed by Shimadzu LC–MS 2010 system. In CCSDD group, during observed 24?h, the mean DEX level in collected samples from highest to lowest following in order: sclera, cornea, retina/choroid, iris, plasma, aqueous humor, lens and vitreous body. In ocular solid tissue, the DEX level in posterior segment is higher than in anatomic corresponding anterior segment, but it is opposite in ocular fluid tissue. High levels of DEX were maintained at 12?h in the ocular tissue immediately after the administration. Even at 24?h, the mean DEX concentration was 31.72?ng/ml and 22.40?ng/ml in aqueous and vitreous, respectively. In CCSDD group, the ocular DEX exposure (AUC_0-24) is much higher and plasma exposure is much less than IV group, and it is also similar in SC group except iris. The amount of DEX levels are markedly increased in ocular tissues but it yield lower plasma levels indicating reduction of systemic absorption by CCSDD. Thus, CCSDD is an effective method of delivering DEX into anterior and posterior segment of the eye.     

Pharmacokinetics of falintolol II. Absorption, distribution and elimination from tissues and organs following ocular administration and intravenous injection of falintolol in albino rabbits

The absorption, distribution and elimination of falintolol maleate was studied in various ocular and extraocular tissues and organs following ocular instillation, intravenous injection of a 0.5% 14C-falintolol ophthalmic solution and repeated ocular instillations of a 1% non-labeled falintolol ophthalmic solution into albino New Zealand rabbits. Falintolol was distributed in all studied tissues and organs after both routes of administration. After ocular instillation, levels of total radioactivity were distinctly higher in ocular tissues than after intravenous injection. Thus, the level was 475 times more important in cornea, 72 times in aqueous humor and 36 times in iris and ciliary body after ocular instillation. On the other hand, levels of total radioactivity in extraocular tissues and organs were 30-50% higher after intravenous injection compared to ocular instillation of the same dose. Peak levels of total radioactivity were generally achieved between 30 min and 1 h after ocular instillation, while 1.5 h after intravenous injection an increase in the declining part of the curve occurred. This increase, characteristic of an enterohepatic reabsorption, was also observed in blood and plasma 1 h after intravenous injection. Urinary elimination was the major means of excretion since 79.6% of total radioactivity was found in urine 6 h after intravenous injection and 74.5% 12 h after ocular instillation. But after ocular instillation, only 5% was excreted as unchanged falintolol. Whatever the route of administration, after single or repeated application, no drug accumulation was evident.     

Calculation of AQCmax: comparison of five ophthalmic fluoroquinolone solutions

ABSTRACT

Objective: Ocular tissue penetration of five different ophthalmic fluoroquinolone solutions in the rabbit eye was measured and evaluated by an index of the maximum aqueous concentration (AQCmax).

Methods: Moxifloxacin 0.5% (MFLX), levofloxacin 0.5% (LVFX), gatifloxacin 0.3% (GFLX), ofloxacin 0.3% (OFLX), or tosufloxacin tosilate 0.3% (TFLX) were instilled into the eyes of white rabbits every 15?min for a total of three doses. Aqueous humor, cornea, iris/ciliary body and vitreous body were collected 10 to 240?min after instillation and drug concentrations were measured by high-performance liquid chromatography.

Results: The concentration of MFLX was the highest in each tissue, with maximum concentrations of MFLX in the aqueous humor (10.16?±?1.59?µg/mL) at 30?min after instillation, cornea (156.07?±?95.97?µg/g) and iris/ciliary body (11.92?±?4.00?µg/g) at 10?min after instillation, and vitreous body (0.099?±?0.033?µg/mL) at 30?min after instillation. The concentration of TFLX was the lowest in each tissue, with LVFX, GFLX, and OFLX sharing the mid-ranks. AQCmax?:?MIC₉₀ ratio for S.?aureus was 150.67 for MFLX, 10.6 for LVFX, 9.69 for GFLX, 3.48 for OFLX, and could not be determined for TFLX.

Conclusion: AQCmax is a useful pharmacokinetic parameter for determining the therapeutic efficacy of an ophthalmic antibiotic, especially when combined with MIC₉₀ values for intraocular pathogens. C_max of MFLX ophthalmic solution was superior in all tissues (cornea, aqueous humor, iris/ciliary body and vitreous body) among the five ophthalmic solutions studied, exceeding the MIC₉₀ of S.?aureus in all tissues, and MIC₉₀s of S.?epidermidis, B.?cereus, and P.?acnes in aqueous humor, cornea, and iris/ciliary body. AQCmax was approximately proportional to C_max in iris/ciliary body and vitreous, and may be used in combination with MIC₉₀s as an index to predict the most appropriate dose and frequency of ophthalmic antibiotics in conjunction with other PK/PD parameters. This study may provide the groundwork for calculation of AQCmax in humans.     

Contribution of different amine oxidases to the metabolism of dopamine in bovine retina.

The contribution of monoamine oxidase (MAO) A, MAO B and semicarbazide-sensitive amine oxidase (SSAO) to the metabolism of dopamine in the bovine retina was studied. These activities were present in the optic nerve, iris, choroid and bovine retina, but they were absent in the lens. SSAO activity towards dopamine was present in the choroid and the retina, but not in the iris or the optic nerve. The corresponding kinetic values for this substrate in the retina and the choroid showed higher affinity for MAO A (Km 271 and 197 microM, respectively) than for MAO B (Km 861 and 404 microM, respectively). This effect was counteracted by the higher Vmax value for MAO B resulting in the Vmax/Km ratio being similar for both cases. The absence of detectable SSAO activity towards dopamine in these last two tissues contrasts with the presence of that enzyme when benzylamine was studied as substrate. These results indicate that two different SSAO activities could be present in the bovine eye.     

Ocular permeation and inhibition of retinal inflammation: an examination of data and expert opinion on the clinical utility of nepafenac

ABSTRACT

Background: The efficacy of topical nonsteroidal anti-inflammatory drugs (NSAIDs) for inflammation in the anterior segment, and pain control after cataract surgery, is well established. However, their effectiveness in the posterior segment has not been as well studied. Nepafenac ophthalmic suspension, 0.1% is a new topical NSAID pro-drug that has been approved by the US Food and Drug Administration (FDA) for the treatment of pain and inflammation after cataract surgery. Preclinical data suggest nepafenac may also provide unique efficacy in the posterior segment.

Scope: We searched the PubMed database from 1966 to 2005 for various combinations of the search terms ‘nepafenac’, ‘ophthalmic’, ‘inflammation’, ‘anterior segment’, and ‘posterior segment’. We review here the three articles identified in the search, and also include findings from three recent clinical trials.

Results: Nepafenac's corneal permeability characteristics are superior to those of ketorolac tromethamine, diclofenac sodium, and bromfenac sodium. Nepafenac is hydrolyzed by intraocular tissues to amfenac, a potent cyclooxygenase inhibitor. In addition to a limited hydrolysis in the cornea, significant bioactivation occurs in the iris/ciliary body and retina/choroid. Nepafenac administration significantly suppresses PGE₂ synthesis in the retina/choroid. Topical nepafenac administration also significantly inhibits prostaglandin (PG)-mediated blood–retinal barrier breakdown and concurrent protein extravasation into the vitreous. In these studies, topical ketorolac and diclofenac failed to inhibit these key markers of inflammation. Nepafenac's clinical effectiveness in the posterior segment may be explained by its superior corneal permeation, biodistribution, and bioactivation to amfenac by the target tissues (i.e., iris, ciliary body, retina, and choroid) known to generate PGs.

Conclusions: Nepafenac's ability to inhibit PG synthesis in the retina/choroid following topical administration indicates the drug also targets suppression of PG synthesis in the posterior segment. Nepafenac may therefore have a clinical role in conditions that are caused by PG-mediated vascular leakage, such as anterior chamber inflammation and cystoid macular edema following cataract surgery.     

Metabolic profiles of difluprednate in rabbit ocular tissues after instillation of difluprednate ophthalmic emulsion

1. Difluprednate (DFBA; 6α,9-difluoro-11β,17,21-trihydroxy-1,4-pregnadiene-3,20-dione 21-acetate 17-butyrate) is an effective anti-inflammatory agent derived from prednisolone. The present study aimed to evaluate the metabolite profile of DFBA in rabbit ocular tissues after instillation of DFBA ophthalmic emulsion.

2. The high-performance liquid chromatography with radiochemical detection was employed to analyze radioactivity in rabbit ocular tissues that had been instilled with a ³H-DFBA 0.05% ophthalmic emulsion. At 0.5 and 2?h after instillation, DFBA was not detected in the cornea, aqueous humor, or iris/ciliary body. Instead, 21-deacetylated DFBA (DFB), 17-debutylated DFB (DF), and an unknown metabolite were found.

3. The unknown metabolite was identified as de-17-side chain-glucocorticoid metabolite (DF21C), which is a novel glucocorticoid metabolite formed by the scission of the 17-side chain via an unknown metabolic reaction pathway. The K_i value of DF21C was 5.6?×?10^?7 mol/L, indicating very weak glucocorticoid receptor binding of DF21C (approximately 1000-fold less than that of DFBA and DFB).

     

Histamine in the rabbit eye: distribution, synthesis, catabolism, and changes by light stimulation

Histamine (HI) is present in all studied ocular (retina, choroid, optic nerve) and brain structures of the albino rabbit. HI levels in neural eye elements (retina and optic nerve) are relatively low, i.e. 70-140 ng/g tissue, and comparable with those found in the brain; a typical vascular tissue, i.e. choroid, contained approximately 10 times more HI. Histadine decarboxylase (HD) activity was found only in brain tissue, while histamine-methyltransferase (HMT) activity was present in all the eye and brain structures. Light stimulation produced changes in HI content only in the retina (decrease) and in the optic nerve (increase).     

A Compartmental Model for the Ocular Pharmacokinetics of Cyclosporine in Rabbits

Studies were conducted in rabbits to determine the ocular distribution and elimination of cyclosporine, with the objective of developing a comprehensive pharmacokinetic model. Following a bolus dose into the anterior chamber, drug levels were measured in the aqueous humor, cornea, iris/ciliary body, lens, sclera, and conjunctiva. Cyclosporine was rapidly eliminated from the aqueous, but drug levels in ocular tissues persisted for in excess of 48 hours, particularly in the cornea and iris/ciliary body. The terminal elimination half life from these tissues was 45 hr and 30 hr, respectively, providing evidence that these tissues could act as a reservoir for the drug. It was found that a compartmental model accurately described the experimental data. A single compartment was used for each of the tissues and fluids sampled, except for the cornea, which was subdivided into two compartments, representing its tissue and aqueous regions.     

Pharmacokinetics and Disposition of Memantine in the Arterially Perfused Bovine Eye

Purpose To develop an improved (¹This is to clearly acknowledge that we have tried to improve an existing model.) arterially perfused bovine eye model and investigate the general ocular disposition of memantine. Materials and Methods Fresh bovine eyes were prepared by exposing and cannulating one ciliary artery, placing the eye into a perfusion chamber and slowly increasing the rate of perfusion to 1.0 ml/min. Analysis of the arterial perfusion pressure (APP), intraocular pressure (IOP), venous perfusate for glucose consumption and lactate dehydrogenase (LDH) activity, and histopathology ensured viability. Memantine was administered with the perfusate (simulated systemic access), by an intravitreal injection and by topical infusion. At the appropriate time points, the cornea, aqueous humour, sclera, iris-ciliary body, choroid/RPE, retina and vitreous humour were harvested and analysed for memantine. Results The preparation remained viable for at least 9 h. At this time, histopathological examination showed mild to moderate deterioration of retinal layers. However, all retinal layers remained well defined and the integrity of the inner limiting membrane and Bruch’s membrane were preserved. Glucose consumption, LDH levels and constant APP and IOP showed that correct cannulation and viability was maintained. After administration, memantine accumulated in the melanin rich iris-ciliary body and choroid/RPE. Results following topical administration indicate that substantial concentrations of memantine are present in the retina and choroid/RPE. Conclusions The arterial perfused bovine eye system proved to be a useful system for ocular drug delivery studies. The experimental results indicate that memantine will accumulate in the posterior segment when delivered by the topical route and that melanin-binding may support sustaining significant concentrations in the retina.     

Development and validation of a fast and sensitive bioanalytical method for the quantitative determination of glucocorticoids—Quantitative measurement of dexamethasone in rabbit ocular matrices by liquid chromatography tandem mass spectrometry

A sensitive, selective, accurate and robust LC–MS/MS method was developed and validated for the quantitative determination of glucocorticoids in rabbit ocular tissues. Samples were processed by a simple liquid–liquid extraction procedure. Chromatographic separation was performed on Phenomenex reversed phase C18 gemini column (50 mm × 4.6 mm i.d.,) with an isocratic mobile phase composed of 30% of acetonitrile in water containing 0.1% of formic acid, at a flow rate 0.2 mL/min. Dexamethasone (DEX), prednisolone (PD) and hydrocortisone (HD) were detected with proton adducts at m/z 393.20 → 355.30, 361.30 → 147.20 and 363.20 → 121.0 in multiple reaction monitoring (MRM) positive mode respectively. Finally, 50 μL of 0.1% novel DEX mixed micellar formulation was topically administered to a rabbit eye and concentrations were measured. The method was validated over a linear concentration range of 2.7–617.6 ng/mL. Lower limit of quantitation (LLOQ) of DEX and PD was measured in the concentration range of 2.7 and 11.0 ng/mL respectively. The resulting method demonstrated intra and inter-day precision within 13.3% and 11.1% and accuracy within 19.3% and 12.5% for DEX and PD, respectively. Both analytes were found to be stable throughout freeze–thaw cycles and during bench top and postoperative stability studies (r² > 0.999). DEX concentrations in various ocular tissue samples i.e., aqueous humor, cornea, iris ciliary body, sclera and retina choroid were found to be 344.0, 1050.07, 529.6, 103.9 and 48.5 ng/mg protein respectively. Absorption of DEX after topical administration from a novel aqueous mixed micellar formulation achieved therapeutic concentration levels in posterior segment of the rabbit eye.     

Ocular permeation and inhibition of retinal inflammation: an examination of data and expert opinion on the clinical utility of nepafenac

BACKGROUND: The efficacy of topical nonsteroidal anti-inflammatory drugs (NSAIDs) for inflammation in the anterior segment, and pain control after cataract surgery, is well established. However, their effectiveness in the posterior segment has not been as well studied. Nepafenac ophthalmic suspension, 0.1% is a new topical NSAID pro-drug that has been approved by the US Food and Drug Administration (FDA) for the treatment of pain and inflammation after cataract surgery. Preclinical data suggest nepafenac may also provide unique efficacy in the posterior segment. SCOPE: We searched the PubMed database from 1966 to 2005 for various combinations of the search terms 'nepafenac', 'ophthalmic', 'inflammation', 'anterior segment', and 'posterior segment'. We review here the three articles identified in the search, and also include findings from three recent clinical trials. RESULTS: Nepafenac's corneal permeability characteristics are superior to those of ketorolac tromethamine, diclofenac sodium, and bromfenac sodium. Nepafenac is hydrolyzed by intraocular tissues to amfenac, a potent cyclooxygenase inhibitor. In addition to a limited hydrolysis in the cornea, significant bioactivation occurs in the iris/ciliary body and retina/choroid. Nepafenac administration significantly suppresses PGE2 synthesis in the retina/choroid. Topical nepafenac administration also significantly inhibits prostaglandin (PG)-mediated blood-retinal barrier breakdown and concurrent protein extravasation into the vitreous. In these studies, topical ketorolac and diclofenac failed to inhibit these key markers of inflammation. Nepafenac's clinical effectiveness in the posterior segment may be explained by its superior corneal permeation, biodistribution, and bioactivation to amfenac by the target tissues (i.e., iris, ciliary body, retina, and choroid) known to generate PGs. CONCLUSIONS: Nepafenac's ability to inhibit PG synthesis in the retina/choroid following topical administration indicates the drug also targets suppression of PG synthesis in the posterior segment. Nepafenac may therefore have a clinical role in conditions that are caused by PG-mediated vascular leakage, such as anterior chamber inflammation and cystoid macular edema following cataract surgery.     

C—硝基吡唑类和C—硝基吡咯类对局部缺血损伤后眼血流量和视网膜功能恢复的作用

AIM: Effects of C-nitropyrazoles and C-nitroazoles on ocular blood flow and retinal .function recovery after ischemia have been studied. METHODS: The compounds were tested on ocular blood flow of ocular hyperten-sive (40 mmHg) rabbit eyes with colored microsphere technique. They were also tested on the retinal function recovery after ischemia of rat eyes with electroretinography. RESULTS: All compounds (DC-1 through DC-17) showed significant increase in retinal function recovery after ischemia in the range of 26 % to 120 % (P<0.05). Among five compounds (DC-1 through DC-5) studied, four compounds (DC-2 through DC-5) in-creased the blood flow in choroid, iris, and ciliary body, but not in retina. DC-1 did not show significant increase of blood flow in any of these ocular tissues. CONCLUSION: C-Nitropyrazoles can facilitate significant retinal function recovery after ischemic insult through the increase of ocular blood flow. Since rabbit's retina is scarce in vasculature, it did not show significant chang     

Ocular hypotensive,vasorelaxant and cyclic AMP intermediation activities of clozapine displaying antiglaucoma properties

Clozapine, an atypical antipsychotic agent with multiple receptor antagonist activities, was investigated in vivo and in vitro to discover its effects on intraocular pressure and blood flow, on the contractility of ciliary muscle and nonophthalmologic blood vessels, on calcium concentration in A7r5 smooth muscle cells, and on cyclic AMP intermediation. The adrenergic and muscarinic mechanisms involved in the above effects were also examined. In rabbits, clozapine (0.1, 0.25, and 0.5%) prolonged (IOP) recovery time and inhibited IOP response. Clozapine (0.1 and 0.25%) also produced a significant increase in ocular blood flow in this iris, ciliary, retina, and choroid at 30 to 180 min after drug administration. In isolated guinea pig thoracic aorta, clozapine relaxed phenylephrine (10 μM)- and KCl (75 mM)-induced contractions, the estimated IC₅₀ values being 20.4 ± 3.1 nM and 10.6 ± 1.8 μM, respectively. Clozapine (0.1–100 μM) inhibited phenylephrine (10 μM)-induced influx of Ca²⁺, the estimated IC₅₀ value being 0.4 ± 0.1 nM. In isolated pig eye ciliary muscles, clozapine (1.0–100 μM) inhibited carbachol (10 μM)-induced contractions, the estimated IC₅₀ value being 5.8 ± 1.2 μM. Clozapine (0.1–100 μM) increased cyclic AMP accumulation in pig's ciliary bodies, including ciliary process, ciliary muscle, and trabecular meshwork. Pretreatment with carbachol (100 μM) first decreased, then increased, clozapine-induced cyclic AMP accumulation. Studies of pretreatments with various muscarinic receptor antagonists at 100 μM revealed that pirenzepine significantly enhanced clozapine (100 μM)-induced cyclic AMP accumulations in trabecular meshwork, while 4-DAMP methiodide inhibited it in ciliary bodies, and methoctramine decreased it in ciliary process. The ocular hypotensive effects of clozapine may be mostly related to its muscarinic agonist/antagonist activities and associated cyclic AMP increasing activities, which lead to ciliary muscle relaxation and a possibly associated increase in uveoscleral outflow. Clozapine's ability to increase blood flow and relax vessels may be attributed to its ability to block α-adrenergic and decrease intracellular calcium. IOP is considered the major cause of glaucoma, and compounds which are capable of reducing IOP are considered useful for glaucoma treatment. Based on the results above, clozapine may potentially be important in the development of new antiglaucoma agents. Drug Dev. Res. 44:163–173, 1998. © 1998 Wiley-Liss, Inc.     

Ocular Toxicity of Experimental Intravitreal Vitamin E

Abstract

Intravitreal injections of DL-alpha tocopherol (vitamin E) oil in doses of 0.05, 0.10, and 0.20 ml were administered to 2–kg pigmented rabbits to determine ocular toxicity. The cornea, lens, iris, and vitreous were examined by slit-lamp biomicroscopy. Indirect ophthalmoscopic and electroretinographic examinations of the retina were performed. Light and electron microscopic examinations of the retina, retinal pigment epithelium, and choroid were obtained. All examinations failed to reveal any ocular toxicity at 1 week, I month, and 3 months after injection of intravitreal vitamin E. Results from this study suggest that administration of vitamin E directly into the vitreous cavity is nontoxic to the eye.     

睫状神经营养因子对大鼠急性高眼压视神经损害的保护作用

目的观察睫状神经营养因子(ciliary neurotrophic factor,CNTF)对大鼠急性高眼压视神经损害的保护作用。方法用平衡盐液前房加压灌注制成大鼠急性高眼压模型,造模前2 d玻璃体内注入CNTF,利用计算机图像分析技术,造模后不同时期观察视神经轴突面积占视神经横截面积百分比。结果CNTF治疗组较对照组视神经轴突面积占视神经横截面积百分比明显增加(P<0.01)。结论CNTF能对急性高眼压视神经损伤提供保护作用。     

Improvement of ocular blood flow with dopamine antagonists on ocular-hypertensive rabbit eyes.

The eyedrops of the ocular-hypotensive dopamine antagonists, trifluperidol, moperone, lenperone, and spiperone, were instilled into an ocular-hypertensive rabbit eye. The blood flows in the choroid, retina, iris root-ciliary body, and iris were measured with colored microspheres at various time periods. It was found that all these dopamine antagonists, at a concentration of 0.5%, increased the blood flow in all eye tissues. Dopamine, at a concentration of 3%, produced a biphasic action by decreasing the blood flow initially at 30 min, then increasing it at 120 min and thereafter. But 1.5% dopamine produced a monophasic action which increased the blood flow after 180 min. Since dopamine antagonists are not cholinergics or adrenolytics, they are not supposed to produce the side effects induced by pilocarpine or timolol. It is hoped that they can become satisfactory drugs for glaucoma and ocular hypertension.