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Biomedical subjects

David Goldblum

Publications and source records attributed to David Goldblum.

At least 19 recordsLinked to original sources
PubMed2007

Noninvasive determination of intraocular pressure (IOP) in nonsedated mice of 5 different inbred strains.

BACKGROUND: Noninvasive intraocular pressure (IOP) measurement in mice is critically important for understanding the pathophysiology of glaucoma. Rebound tonometry is one of the methods that can be used for obtaining such measurements. We evaluated the ability of the rebound tonometer (RT) to determine IOP differences among various mouse strains and whether differences in corneal thickness may affect IOP measurements in these animals. MATERIALS AND METHODS: Five different commonly used mouse strains (BALB/C, CBA/CAHN, AKR/J, CBA/J, and 129P3/J) were used. IOP was measured in eyes from 12 nonsedated animals (6 male and 6 female) from each strain at 2 to 3 months of age using the RT. IOPs were measured in all animals, on 2 different days between 10 AM and 12 PM. Subsequently, a number of eyes from each strain were cannulated to provide a calibration curve specific for that strain. Tonometer readings for all strains were converted to apparent IOP values using the calibration data obtained from the calibration curve of the respective strain. For comparison purposes, IOP values were also obtained using the C57BL/6 calibration data previously reported. IOP for the 5 strains, male and female animals, and the different occasion of measurement were compared using repeat measures analysis of variance. The central corneal thickness (CCT) of another group of 8 male animals from each of the 5 strains was also measured using an optical low coherence reflectometry (OLCR) pachymeter modified for use with mice. CCT values were correlated to mean IOPs of male animals and to the slopes and intercept of individual strain calibration curves. RESULTS: Noninvasive IOP measurements confirm that the BALB/C strain has lower and the CBA/CAHN has higher relative IOPs than other mouse strains while the AKR/J, the CBA/J, and the 129P3/J strains have intermediate IOPs. There is a very good correlation of apparent IOP values obtained by RT with previously reported true IOPs obtained by cannulation. There was a small but statistically significant difference in IOP between male and female animals in 2 strains (129P3/J and AKR/J) with female mice having higher relative IOPs. No correlation between CCT and IOP was detected. CCT did not correlate with any of the constants describing the calibration curves in the various strains. CONCLUSIONS: Noninvasive IOP measurement in mice using the RT can be used to help elucidate IOP phenotype, after prior calibration of the tonometer. CCT has no effect on mouse IOP measurements using the RT.

Animals↗
PubMed2006

Ocular penetration of caspofungin in a rabbit uveitis model.

BACKGROUND: Little is known about the ocular penetration of echinocandin antifungals. We studied the ocular distribution of systemically administered caspofungin in a rabbit uveitis model. METHODS: Caspofungin (1 mg/kg per day) was given intravenously to rabbits as a single dose or as repeated daily doses on 7 days starting 24 h after induction of unilateral uveitis by intravitreal endotoxin injection. Caspofungin concentrations were determined by high-performance liquid chromatography in the cornea, aqueous humor, vitreous humor, and serum 4, 8, 16, and 24 h after administration of a single dose and 24 h after the last of seven doses. RESULTS: The mean caspofungin concentration in the aqueous of the inflamed eye 4 and 8 h after single-dose administration was 1.30 +/- 0.39 microg/ml and 1.12 +/- 0.34 microg/ml, respectively. Drug concentrations decreased to 0.24 +/- 0.09 microg/ml at 16 h and 0.26 +/- 0.14 microg/ml at 24 h. In the vitreous of inflamed eyes drug levels were undetectable at all time points. No drug was found in the aqueous of inflamed eyes 24 h after the last of seven repeated doses, and the vitreous only contained trace amounts. In the corneas of inflamed eyes concentrations reached 1.64 +/- 0.48 microg/g at 4 h, peaked at 2.16 +/- 1.14 microg/g at 8 h, and declined to 1.87 +/- 0.52 microg/g and 1.49 +/- 0.48 microg/g at 16 and 24 h, respectively. After repeated dosing, corneal concentrations of caspofungin were 0.8 and 1.0 microg/g and below the limit of detection in two of four animals. In non-inflamed eyes no drug was detectable in the aqueous and vitreous humor, and the corneas at any time point. CONCLUSIONS: In our model, caspofungin reached therapeutically relevant levels in the aqueous and cornea but not in the vitreous humor of inflamed eyes. Intraocular drug deposition was critically dependent on a disrupted blood-eye barrier. These findings suggest a limited role for caspofungin in the treatment of fungal endophthalmitis.

Animals↗
PubMed2006

Effect of oral donepezil on intraocular pressure in normotensive Alzheimer patients.

Donepezil, a selective acetylcholinesterase (AChE) inhibitor, has been shown to reduce intraocular pressure (IOP) in ocular normotensive rabbit eyes. The aim of this investigation was to evaluate the effect of oral donepezil on IOP and pupil diameter after mid-term oral treatment in normotensive persons. Thirty-two newly diagnosed Alzheimer patients with normal IOP and no further antiglaucomatous treatment were included in the study. IOP and pupil diameter were evaluated before and 4 weeks after daily intake of 5 mg donepezil. IOP and pupil diameter were significantly lower/smaller after 4 weeks of treatment. The mean IOP of all 63 eyes was 14.1 mmHg before and 12.8 mmHg after treatment (8.8% reduction). Mean pupil diameter constricted from 3.9 to 3.6 mm (-7.4%). These findings show that donepezil, and, possibly, other selective AChE inhibitors, can potentially be used to treat glaucoma. They are also known to have neuroprotective effects in Alzheimer's, and, therefore, might have an additional therapeutic benefit.

Administration, Oral↗
PubMed2005

Characterization of retinal damage in the episcleral vein cauterization rat glaucoma model.

Episcleral vein cauterization (EVC) is used in rats to generate a glaucoma model with high intraocular pressure (IOP). The long-term retinal damage in this glaucoma model, however, has not been accurately quantified. We report the location and amount of retinal ganglion cell (RGC) damage caused by (EVC) induced IOP elevation in two rat strains. IOP was raised in one eye of Wistar (N = 5) and Brown-Norway(B-N)(N = 7) rats by EVC and monitored monthly until IOP in contralateral eyes equalized at 5 months post-surgery. Animals were maintained for 3.5-4.5 additional months. B-N rats (N = 7) that had no EVC served as controls for this strain. Scotopic flash ERGs were recorded at baseline and just prior to euthanasia. Automated counts of all retrogradely labeled RGCs in retinal flat-mounts were determined and compared between contralateral eyes. RGC density maps were constructed and RGC size distribution was determined. Oscillatory potentials in the group of eyes which had elevated IOP were decreased at the time of euthanasia, when IOP had returned to normal. The group of normal B-N rats had similar RGC counts between contralateral eyes. In the experimental group the mean number of RGCs was not significantly different between control and experimental eyes, but 1 of 5 Wistar and 2 of 7 B-N experimental eyes had at least 30% fewer RGCs than contralateral control eyes. Total retinal area in B-N experimental eyes was higher compared to contralateral eyes. Cumulative IOP exposure of the experimental eyes was modestly correlated with RGC loss while oscillatory potentials appeared to be inversely related to RGC loss. In retinas with extensive (> 30% RGC loss) but not complete damage, smaller cells were preserved better than larger ones. The above results indicate that RGC loss in both Wistar and B-N strains is variable after a prolonged elevation of IOP via EVC. Such variability despite equivalent IOP levels and ERG abnormalities, suggests unknown factors that can protect IOP-stressed RGCs. Identification and enhancement of such factors could prove useful for glaucoma therapy.

Animals↗
PubMed2005

Effects of daunorubicin, mitomycin C, azathioprine and cyclosporin A on human retinal pigmented epithelial, corneal endothelial and conjunctival cell lines.

BACKGROUND: We wished to investigate the toxicity of four immunosuppressant and antimetabolic drugs, which are known to influence postoperative wound healing, on three different human ocular cell lines. METHODS: Acute toxicity to cyclosporin A, azathioprine, mitomicyn C and daunorubicin was assessed in Chang cells by monitoring their uptake of propidium iodide during a 3-h period. Chronic toxicity was assessed by monitoring the proliferation and viability of subconfluent cultures of Chang cells, human corneal endothelial cells (HCECs) and retinal pigmented epithelial (RPE) cells after continuous exposure to the drugs for 7 days. RESULTS: Acute toxicity testing revealed no obvious effects. However, the chronic toxicity tests disclosed a narrow concentration range over which cell proliferation decreased dramatically but calcein metabolism was sustained. Although the three lines reacted similarly to each agent, HCECs were the most vulnerable to daunorubicin and mitomycin. At a daunorubicin concentration of 0.05 microg/ml, a 75% decrease in calcein metabolism (P < 0.001) and a > or = 95% cell loss (P < 0.001) were observed. At a mitomycin concentration of 0.01 mug/ml, cell density decreased by 61% (P < 0.001) without a change in calcein metabolism, but at 0.1 microg/ml, the latter parameter decreased to 12% (P = 0.00014). At this concentration the proliferation of Chang and RPE cells decreased by more than 50%, whilst calcein metabolism was largely sustained. Cyclosporin inhibited cell proliferation moderately at lower concentrations (< 5 microg/ml; P=0.05) and substantially at higher ones, with a corresponding decline in calcein metabolism. Azathioprine induced a profound decrease in both parameters at concentrations above 5 microg/ml. CONCLUSION: Daunorubicin, cyclosporin and azathioprine could be used to inhibit excessive intraocular scarring after glaucoma and vitreoretinal surgery without overly reducing cell viability. The attributes of immunosuppressants lie in their combined antiproliferative and immunomodulatory effects.

Antimetabolites↗
PubMed2005

Tocotrienol inhibits proliferation of human Tenon's fibroblasts in vitro: a comparative study with vitamin E forms and mitomycin C.

PURPOSE: To evaluate the potential of the vitamin E compound alpha-tocotrienol as antifibrotic agent in vitro. METHODS: Using human Tenon's capsule fibroblast cultures, the antiproliferative and cytotoxic effects of the different vitamin E forms alpha-tocopherol, alpha-tocopheryl acetate, alpha-tocopheryl succinate and alpha-tocotrienol were compared with those of mitomycin C. To mimic subconjunctival and regular oral application in vivo, exposure time of serum-stimulated and serum-restimulated fibroblasts (SF and RF, respectively) to vitamin E forms was set at 6 days. Cultures were only exposed for 5 min to mitomycin C due to its known acute toxicity and to mimic the short-time intraoperative administration. Proliferation (expressed as % of control) was determined by DNA content quantification on days 2, 4 and 6, whereas cytotoxicity was assessed by cell morphology and glucose 6-phosphate dehydrogenase (G6PD) release after 24 h. RESULTS: alpha-Tocopherol and alpha-tocopheryl acetate stimulated growth of SF, but not RF. Reduction of fibroblast content by alpha-tocopheryl succinate was accompanied by increased G6PD release and necrosis. Contrary to alpha-tocopheryl succinate, 50 microM or repeatedly 20 microM of alpha-tocotrienol significantly inhibited proliferation without causing cellular toxicity (maximal effect: 46.8%). RF were more sensitive to this effect than SF. Mitomycin C 100-400 microg/ml showed a stronger antiproliferative effect than alpha-tocotrienol (maximal effect: 13.8%). Morphologic characteristics of apoptosis were more commonly found under treatment with mitomycin C. CONCLUSIONS: Of the vitamin E forms tested, only alpha-tocotrienol significantly inhibited growth at non-toxic concentrations. In this in vitro study, antiproliferative effects of mitomycin C were stronger than those of alpha-tocotrienol.

Aged↗
PubMed2005

Topical caspofungin for treatment of keratitis caused by Candida albicans in a rabbit model.

Candida albicans is the most frequent cause of fungal keratitis in temperate regions. Caspofungin has potent activity against Candida spp. in a variety of clinical settings. Little is known, however, about its activity against fungal keratitis. We compared the efficacy of topical caspofungin with that of topical amphotericin B (AMB) in a rabbit model of experimental keratomycosis. Keratitis was induced with a standardized inoculum of Candida albicans (SC 5314) placed on the debrided cornea. Twenty-four hours after infection, animals were randomly assigned to treatment with 0.15% caspofungin, 0.5% caspofungin, 0.15% AMB, and a saline control (n = 12 rabbits in each group). For the first 12 h, treatment was repeated every 30 min and, after a 12-h pause, was resumed at hourly intervals for another 12 h. The animals were examined and killed 12 h after administration of the last dose. Treatment effects were evaluated by clinical assessment, fungal culture, and histopathology. Drug treatment significantly reduced corneal fungal recovery from 3.78 log10 CFU in saline-treated animals to 2.97, 1.76, and 1.18 log10 CFU in animals treated with 0.15% caspofungin, 0.5% caspofungin, and 0.15% AMB, respectively. By histopathology, the mean hyphal density was significantly lower in the corneas of treated animals than in those of the controls; there was no difference in hyphal densities between the different treatment groups. The depth of corneal invasion was not significantly reduced by the antifungal treatments. By clinical assessment, keratitis progressed in animals treated with saline, whereas disease progression was inhibited by all drug treatment regimens. In our rabbit model, 0.5% caspofungin was as effective as 0.15% AMB for the topical treatment of Candida keratitis. The potential clinical efficacy of caspofungin awaits further investigation.

Administration, Topical↗
PubMed2003

In vivo pachymetry in normal eyes of rats, mice and rabbits with the optical low coherence reflectometer.

The aim of this study was to determine the central corneal thickness (CCT) in living rats, mice and rabbits using a non-contact, high-speed optical low coherence reflectometer (OLCR) mounted on a regular slit lamp. Both eyes of eight male Wistar rats, eight male balb-c mice and eight male Japanese rabbits were measured. Each eye was measured twice (one measurement consists of 20 scans), the average calculated. Additionally, CCT was measured in rabbits using an ultrasound pachymeter. The mean CCT was: RATS: 159.08 microm (SD+/-14.99 microm), MICE: 106.0 microm (SD+/-3.45 microm) and RABBITS: 356.11 microm (SD+/-14.34 microm). With the use of OLCR we were able to accurately measure the CCT of rats, mice and rabbits in vivo. This technique may prove useful in further refractive, pharmacological and glaucoma studies.

Animals↗
PubMed2003

[Eye injuries caused by "Hornussen"--a traditional Swiss team game].

BACKGROUND: "Hornussen" is a traditional Swiss team game played in rural areas of Switzerland. A puck made out of hard plastic called "Hornuss" or "Nouss" is hit with a lash like racket into the field. The opposing team has to capture the flying puck with shovel like shields. Eye injuries are rare, however, very severe. PATIENTS: We report on three patients who were seen and treated at the university eye clinic Berne in the last four years. RESULTS: All injuries were blunt contusions with involvement of the periorbital soft tissues by a hit with the "Hornuss". In two cases orbital fractures were observed and in one case there was a rupture of the globe in a pre-injured aphakic eye. Only in one case was there a direct hit to the eye by the "Hornuss", the other injuries were caused by indirect hit after the "Hornuss" bounced off the shovel like shields. No protection gear was used. One patient showed complete recovery, whereas in the other two cases significant impairment remained. CONCLUSIONS: Without adequate protection gear, injuries caused by "Hornussen" are generally severe. The injury pattern with periorbital involvement resembles eye injuries caused by baseballs. This is probably due to the similar size of the balls. The mandatory wearing of protection helmets issued by the federal "Hornusser" association for young players should be extended as a general requirement for all players.

Adult↗
PubMed2003

[Penetrating keratoplasty in Down's syndrome].

BACKGROUND: Purpose of this retrospective study was to analyze outcome and complications after penetrating keratoplasty (PK) in patients with Down's syndrome. PATIENTS AND METHODS: The medical records of all patients with Down's syndrome and PK from 1985 were reviewed retrospectively. Age, sex, systemic diseases, communication, indication for surgery and surgical technique, age at first PK, complications, visual acuity and best corrected visual acuity and findings at last follow-up were noted. Age matched mentally non-retarded patients with keratoconus and PK served as a control group. RESULTS: All eyes of 9 patients had keratoconus, 16 were operated. Indication for surgery was spontaneous perforation in 3 and refractive in the remaining 13 eyes. Five grafts were clear at last follow-up. In 7 eyes, at least 1 re-PK had to be performed. Seven eyes developed graft rejection and 4 eyes needed conjunctival grafting because of non-healing epithelial defects. Ten eyes developed cataracts, 3 secondary glaucoma. In the control group 22 out of 25 operated corneas were clear at last follow-up. CONCLUSIONS: Prognosis of PK in patients with Down's syndrome is worse than in other patients with keratoconus. Poor results are not only explained due to the lack of cooperation of patients, but also because of: 1) high rate of emergency procedures (3/16), 2) presence of lid anomalies and 3) very advanced keratoconus, necessitating bigger sized grafts, leading to frequent immunological reactions, suture loosening and secondary glaucoma. Indication for PK in Down's syndrome patients with keratoconus and floppy eyelids should be very restrictive. Postoperative complications and the high rejection rate might be decreased by performing deep lamellar keratoplasty as this would not be an intraocular procedure.

Adult↗
PubMed2003

Quantitative analysis of retinal ganglion cell (RGC) loss in aging DBA/2NNia glaucomatous mice: comparison with RGC loss in aging C57/BL6 mice.

PURPOSE: To quantify the extent and pattern of retinal ganglion cell (RGC) loss in the DBA2/NNia glaucomatous mouse strain as a function of age and compare it with ganglion cell loss in a nonglaucomatous strain. METHODS: All the ganglion cells in retinas of DBA/2NNia and C57/BL6 mice of various ages (five eyes per age group in 3-month intervals from 3 to 18 months of age) were counted. A novel counting method that does not rely on sampling and that uses retrograde labeling of RGCs with Fluorogold (Fluorochrome; Englewood, CO) was used. RGC loss in the glaucomatous DBA/2NNia mouse strain was contrasted to RGC loss in C57 mice at the same ages. The total number of Fluorogold-labeled cells per retina was compared within and among the two strains as a function of age. In addition, RGC density maps were constructed for each retina, and the range of densities for each age group was compared within and among the two strains. IOP in awake, nonsedated DBA/2NNia mice was measured with a rebound tonometer. RESULTS: RGC loss started between 12 and 15 months of age in C57 mice and led to an approximate 46% reduction by 18 months of age. The rate of loss was best approximated by a second-order polynomial curve. In comparison, DBA/2NNia mice also began showing RGC loss at approximately 12 months of age, but it proceeded at a much faster rate, with approximately 64% of their RGCs dying by the 15th month of age but little additional loss thereafter. RGC loss in the DBA animals had a focal pattern that appeared more patchy and showed greater variability than the age-related loss in C57 mice, which was more diffuse. IOP and total retinal area in DBA/2NNia mice began to increase at approximately 6 months of age. IOP normalized after the 12th month of age. CONCLUSIONS: Age-related RGC loss of up to 50% can occur in the C57 mouse by 18 months of age. The loss does not proceed linearly with age, as is often assumed, and differs both in extent and locational pattern from pathologic RGC loss secondary to glaucoma in DBA/2NNia mouse retinas.

Aging↗
PubMed2002

Non-invasive determination of intraocular pressure in the rat eye. Comparison of an electronic tonometer (TonoPen), and a rebound (impact probe) tonometer.

BACKGROUND: The reproducibility and accuracy of the induction/impact (I/I) probe device (rebound tonometer) and the TonoPen XL electronic tonometer were compared through the measurement of intraocular pressure (IOP) differences between contralateral rat eyes. METHODS: IOP was measured in 18 female Wistar rats with variable, modest elevations of IOP in one eye. Mean IOP from five measurements on each of the 36 eyes was determined using the rebound tonometer, followed by the TonoPen XL. Following cannulation, true (manometrically determined) IOP was recorded with a calibrated pressure transducer. Differences between the operated and normal eye of each animal for each tonometric method of measurement were correlated with the true difference in IOP. RESULTS: IOP differences between the operated and contralateral normal eye ranged from +5.9 to -1.7 mmHg (mean +1.7 mmHg) when measured by cannulation and from +7.2 to -1.4 mmHg (mean +2.4 mmHg) and +9.8 to -3.2 mmHg (mean +3.6 mmHg) when measured with the rebound tonometer and TonoPen XL respectively. Differences between eyes recorded by rebound tonometer ( y) correlated with those determined by cannulation ( x) in a linear fashion ( y=0.8243 x+1.0721; R(2)=0.6603). Correlation for the TonoPen XL was much weaker ( y=0.8675 x+2.1672; R(2)=0.2077). IOP measurements using the rebound tonometer did not differ significantly from true IOP, whereas TonoPen XL increasingly underestimated IOP with increasing IOP (9-20 mmHg). CONCLUSION: The rebound tonometer displayed greater accuracy and less variability than TonoPen XL in measuring the IOP of the rat eye (range 9-20 mmHg).

Animals↗
PubMed2002

Association between sleep apnea syndrome and nonarteritic anterior ischemic optic neuropathy.

OBJECTIVE: To determine if patients with nonarteritic ischemic optic neuropathy (NAION) have sleep apnea syndrome (SAS), an entity characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption. METHODS: We recruited 17 patients with NAION and 17 age- and sex-matched controls from patients referred for treatment because of suspected restless legs syndrome. We performed overnight polysomnography and determined the respiratory disturbance index during night sleep, a value used to diagnose and grade SAS. We compared the proportions of patients with SAS among patients with NAION and matched controls using the chi(2) test. Additionally, we compared the proportions of patients with SAS among patients with NAION and a large SAS prevalence study using the binomial test. RESULTS: Twelve (71%) of 17 patients with NAION had SAS. According to the respiratory disturbance index, 4 patients (24%) had mild, 4 patients (24%) had moderate, and 4 patients (24%) had severe SAS. Only 3 (18%) of 17 controls had SAS (P =.005). In the 45- to 64-year age group, 4 (50%) of 8 patients with NAION had SAS; 51 (11.9%) of 430 of the random sample in the prevalence study had SAS (P =.005). In the group older than 64 years, 8 (89%) of 9 patients with NAION had SAS; 18 (24%) of 75 of the random sample in the prevalence study had SAS (P<.001). CONCLUSIONS: We found a high prevalence of SAS in patients with NAION, which supports previous case reports suggesting that such an association exists. This association may explain why approximately 75% of all patients with NAION discover visual loss on first awakening or when they first use vision critically after sleeping. Our findings indicate that SAS may play an important role in the pathogenesis of NAION.

Aged↗
PubMed2002

Prospects for relevant glaucoma models with retinal ganglion cell damage in the rodent eye.

Retinal ganglion cell (RGC) death is the end result of practically all diseases of the optic nerve, including glaucomatous optic neuropathy. Understanding the factors determining susceptibility of the retina or the optic nerve to glaucomatous damage, and the means to prevent it, requires good animal models. Here we review the different, current models in rodents that have been used to study RGC damage, discuss their value, and their adequacy as models for human glaucoma.

Acute Disease↗
PubMed2002

Ocular distribution of intravenously administered lipid formulations of amphotericin B in a rabbit model.

Little is known about the ocular penetration of amphotericin B (AMB) and its lipid formulations, the current drug of choice in fungal endophthalmitis. The ocular distribution of AMB lipid complex (ABLC), liposomal AMB (L-AMB), and AMB deoxycholate (D-AMB) was studied in a rabbit model. D-AMB (1 mg/kg of body weight/day), ABLC (5 mg/kg/day), or L-AMB (5 mg/kg/day) was given intravenously to rabbits as a single dose or as repeated daily doses on 7 consecutive days after induction of unilateral uveitis by intravitreal injection of endotoxin. AMB concentrations in aqueous humor, vitreous humor, and plasma were determined by high-pressure liquid chromatography 16 h after administration of a single dose or 24 h after the last of seven doses. After single-dose administration, L-AMB achieved at least eightfold-higher AMB concentrations in the aqueous of inflamed eyes than ABLC or D-AMB (1.21 +/- 0.58 micro g/ml versus 0.14 +/- 0.04 and 0.11 +/- 0.09 micro g/ml, respectively). At that time point no drug was detectable in the vitreous. After 7 days of treatment, the concentration of AMB in the vitreous was higher after treatment with L-AMB (0.47 +/- 0.21 micro g/ml) than after treatment with ABLC (0.27 +/- 0.18 micro g/ml) and D-AMB (0.16 +/- 0.04 micro g/ml). Similarly, AMB concentration in the aqueous was higher after repeated doses of L-AMB (0.73 +/- 0.43 micro g/ml) than after repeated doses of ABLC (0.03 +/- 0.02 micro g/ml) or D-AMB (0.13 +/- 0.06 micro g/ml). No AMB was detected in noninflamed eyes. Following systemic administration, AMB distribution to the eye is inflammation dependent and occurs sequentially, first to the aqueous and then to the vitreous. Compared to D-AMB and ABLC, L-AMB reaches higher drug concentrations in both ocular compartments.

Amphotericin B↗
PubMed2002

Cytoarchitecture of the retinal ganglion cells in the rat.

PURPOSE: To determine the number and cytoarchitecture of retinal ganglion cells (RGCs) in the female Wistar rat, by using a newly devised procedure for rapid RGC counting in the entire retina that avoids assumptions about RGC spatial arrangement. METHODS: RGCs of normal female Wistar rats were retrogradely labeled with a fluorescent tracer. Automated counting was accomplished by applying standard imaging software to analysis of all labeled cells in retinal flatmounts. The method was validated by comparison of automated and manual counts of 70,000 RGCs in frames covering the density range in the normal rat retina of 600 to 3600 RGC/mm(2). RGC numbers were determined for each retina and compared with the contralateral retina of the same animal. RGC density maps were constructed for each retina. RGC size distribution was determined. RESULTS: Automated RGC counting showed a good linear correlation with manual counting (R(2) = 0.9416). Mean total RGC count in 10 rat eyes was 97,609 +/- 3,930 (SEM) per eye. Contralateral eyes differed by an average of 4.1% (3983 plus minus 5098 RGCs). Size analysis calculated from cell areas confirmed that the majority of rat RGCs are between 7 and 21.5 microm in equivalent diameter. The RGC counts for all frames at the same eccentricity in all 10 of the retinas showed that variability increased with eccentricity and increased further as the fractional area of the retina sampled at each eccentricity was reduced. There was also significant variability in the spatial density of the RGCs at the same eccentricity location between different eyes. Comparison of total RGC counts between left and right eyes estimated from RGC counts in sectors of the retina (hemiretinas or quadrants) showed increased variability compared with counting all the RGCs in a retina. CONCLUSIONS: RGCs in the Wistar rat display significant variability in their cytoarchitecture. Such variability can make quantification by sampling problematic for diffuse, and particularly, for focal RGC losses resulting from experimental interventions, unless virtually the entire RGC population is counted.

Animals↗