Olav Mäepea

Pressures in the juxtacanalicular tissue and Schlemm's canal in monkeys

A micropuncture technique involving the use of microcannulas with tip diameters less than 5 microns was used to measure the pressure in Schlemms canal and in the meshwork at distances approximately 7 and 14 microns from the inner wall of Schlemms canal. In one set of experiments where the spontaneous intraocular pressure (IOP) was 12.2 +/- 0.5 cmH2O and the Schlemms canal pressure (PSc) was 7.6 +/- 0.7 cmH2O, the pressure at 7 microns from the inner wall of Schlemms canal was found to be 8.9 +/- 0.7 cmH2O and at a distance of 14 microns, 11.0 +/- 0.5 cmH2O--that is, 1.3 +/- 0.2 and 3.4 +/- 0.3 cmH2O respectively, higher than the PSc. In another set of experiments, the spontaneous IOP and PSc were also measured and then the IOP was increased by means of an external reservoir and measured once again. Spontaneous IOP was 16.0 +/- 1.3 cmH2O and the PSc was 11.5 +/- 1.4 cmH2O before the IOP was increased. After the IOP was increased to 20.2 +/- 1.2 cmH2O, the PSc was 11.7 +/- 1.6 cmH2O. When the microcannula was introduced into the juxtacanalicular tissue to locations at about 7 and 14 microns from the inner wall of Schlemms canal the pressure measured at 7 microns was 16.9 +/- 1.3 and at 14 microns it was 18.9 +/- 1.4 cmH2O--that is, 5.2 +/- 0.8 and 7.2 +/- 1.0 cmH2O respectively, higher than the PSc. The results indicate that at the spontaneous IOP about 75% of the resistance between the anterior chamber and Schlemms canal is located within 14 microns from the canal with some 50% being located within the region 7 and 14 microns from the canal. After a small increase in IOP, the tissue causing most of the outflow resistance became relocated to a region within 7 microns from the canal.

The pressures in the episcleral veins, Schlemm's canal and the trabecular meshwork in monkeys: Effects of changes in intraocular pressure

The pressures in the episcleral veins, Schlemms canal and the trabecular meshwork were studied with a micropuncture technique using cannulas with tip diameters of less than 5 microns. The pressure in Schlemms canal, Psc, was 14.3 +/- 1.0 cmH2O at spontaneous intraocular pressure, IOP, 19.2 +/- 0.9 cmH2O. The outflow pressure from the anterior chamber to Schlemms canal was 4.9 +/- 0.7 cmH2O. The relationship between pressures was IOP = 0.73 Psc + 8.7. When the intraocular pressure was increased stepwise from the spontaneous level to 30 cmH2O there was an increase in pressure in Schlemms canal of 1.7 +/- 0.6 cmH2O, (P less than 0.05). The total outflow resistance and the resistance between the anterior chamber and Schlemms canal were 3.27 +/- 0.43 and 2.92 +/- 0.50 cmH2O min microliter-1 respectively for the intraocular pressure interval between the spontaneous pressure and a level 4-11 cmH2O higher. In the intraocular pressure range from 20 to 30 cmH2O the corresponding figures were 2.89 +/- 0.45 and 2.69 +/- 0.42 cmH2O min microliter-1 and for the pressure range 25-35 cmH2O, 2.48 +/- 0.58 and 2.31 +/- 0.59 cmH2O min microliter-1. The difference between the total outflow resistance and that between the anterior chamber and Schlemms canal was about 10% of the total at intraocular pressures below 35 cmH2O. Stepwise increments in IOP increased the trabecular meshwork pressure by 0.88 cmH2O for each cmH2O increase in IOP in the interval of 30-50 cmH2O. The total outflow resistance and the resistance between the anterior chamber and the tip of the microcannula was 3.91 +/- 1.53 and 1.94 +/- 0.99 cmH2O min microliter-1 respectively for the intraocular pressure interval between the spontaneous pressure and 30 cmH2O. In the interval between 30 and 45 cmH2O the corresponding figures were 2.16 +/- 0.66 and 0.20 +/- 0.13 cmH2O min microliter-1. The episcleral venous pressure at the spontaneous intraocular pressure was 14.1 +/- 1.0 cmH2O in seven animals with minimal trauma, and 12.3 +/- 0.8 cmH2O in animals after cannulation of Schlemms canal. The outflow pressure from the anterior chamber to the episcleral veins was 4.4 +/- 1.2 cmH2O in animals with minimal trauma and 7.1 +/- 0.8 cmH2O after cannulation of Schlemms canal. The relationship between pressures was IOP = 0.68EVP + 11.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of atrial natriuretic factor (ANF) on intraocular pressure and aqueous humor flow in the cynomolgus monkey

Atrial natriuretic factor (ANF: human sequence) was examined for its effects on basal and terbutaline-stimulated aqueous humor flow, intraocular pressure (IOP) and uveoscleral outflow in cynomolgus monkeys under pentobarbital anesthesia. A dilution method with radioactively labeled albumin was used for the determination of aqueous humor flow. ANF was given by i.v. infusion or intracamerally. Intracameral administration of terbutaline increased the aqueous humor flow significantly; 1.10 +/- 0.05 microliter min-1 in the control eye and 1.69 +/- 0.06 microliter min-1 in the treated eye. I.v. infusion of ANF, 97 fmol kg-1 min-1, increased the aqueous humor flow by about 44% from basal values in the control eye. There was a small but not statistically significant increase on the terbutaline-treated side. The IOP was not changed by ANF at this dose. An ANF dose of 97 pmol kg-1 min-1 increased the aqueous humor flow by 51% in the control eye and by 19% in the terbutaline-treated eye. A further rise of about 8% in aqueous humor flow was registered on the control side when the infused ANF-dose was doubled. Doubling the dose also resulted in a decrease of the IOP by 1.3 +/- 0.3 mmHg on the control side and 2.2 +/- 0.4 mmHg on the terbutaline-stimulated side. Intracameral administration of ANF (81-162 pmol ml-1 perfusion fluid) increased the aqueous humor flow transiently by approximately 50% with a maximum after about 2 hr. The uveoscleral outflow tended to increase and IOP tended to decrease in the ANF-treated eye compared with the control. However, these effects were not statistically significant. These results suggest that ANF may be involved in the control of aqueous humor formation.

Effects of timolol on terbutaline- and VIP-stimulated aqueous humor flow in the cynomolgus monkey

The effects of timolol on terbutaline- and VIP-stimulated aqueous humor flow were investigated in cynomolgus monkeys, with a labeled albumin dilution method. The maximal increase in aqueous humor flow caused by intracameral (100 micrograms/ml) or intravenous (0.4 micrograms/kg/min) administration of terbutaline was about 100%. The effect of intravenously infused terbutaline was completely abolished by intracameral administration of timolol, 0.1 mg/ml. The same dose of timolol also abolished the effect of intravenously infused VIP, 50 ng/kg/min. Intravenous administration of timolol, 0.2 mg/kg, had no effect on VIP-stimulated aqueous humor flow, when VIP (90 micrograms) was given intracamerally, but abolished completely the effect of intracameral terbutaline, 100 micrograms/ml. The results suggest that the effect of intravenously infused VIP on aqueous humor flow is secondary to activation of the sympathetic nervous system, while the effect of intracameral administration of VIP is a direct effect on the ciliary epithelium. The maximal aqueous humor flow achieved with terbutaline is comparable to that in conscious cynomolgus monkeys.

Ocular blood flow in experimental glaucoma: a study in cynomolgus monkeys.

Experimental glaucoma was induced in 1 eye of 6 cynomolgus monkeys by laser treatment of the trabecular meshwork. In 5 of the 6 monkeys the increased intraocular pressure (IOP) caused marked glaucomatous damage in the experimental eye. Ocular blood flow was determined with labeled microspheres 4 years after the laser treatment. IOP was regulated with an external reservoir. With the same perfusion pressure in both eyes no statistically significant difference was observed between the 2 eyes for total ocular blood flow or for blood flow through any of the ocular tissues. Total ocular blood flow was 343.5 +/- 61.4 mg/min (mean +/- SEM) in the control eye and 385.3 +/- 107.7 mg/min in the experimental eye.

CHOLINE TRANSPORT THROUGH THE BLOOD-RETINAL AND THE BLOOD-BRAIN BARRIER IN VIVO

The uptake index method was used to study retinal and cerebral uptake of [14H]labelled choline in rats. In both tissues a saturable uptake was observed. This uptake was significantly inhibited by 10–20 mM unlabelled choline chloride as well as by 10 mM hemicholinium‐3. It is concluded that choline passes the blood‐retinal barrier by a carrier‐mediated transport system similar to that in the blood‐brain barrier.

Suppression of VIP-and terbutaline stimulated aqueous humor flow by increased intraocular pressure in the cynomolgus monkey

The effect of increased intraocular pressure (IOP) on stimulated aqueous humor flow (AHF) was studied in cynomolgus monkeys. Two experimental series were performed, one with unilateral VIP-treatment (60 micrograms intracamerally) and one with unilateral terbutaline-treatment (10 micrograms.ml-1 perfusion fluid). The AHF was determined with a labelled albumin dilution method, and an artificial increase in IOP was produced by clamping the outlet of the perfusion system, thus causing a net inflow of perfusion fluid. The initial AHF was significantly higher in the VIP-treated eye than in the control eye - 1.568 +/- 0.095 as compared to 1.112 +/- 0.103 microliters.min-1 (P less than or equal to 0.01). The spontaneous IOP was 5.8 +/- 0.4 mmHg (P less than or equal to 0.001) higher in the VIP-treated eye. There was no difference in pseudofacility between the VIP-treated eye (0.063 +/- 0.016 microliter.min-1.mmHg-1) and the control eye (0.065 +/- 0.022 microliter.min-1.mmHg-1), but the total and true outflow facilities were higher in the VIP-treated eye. In the experiments with terbutaline, the initial AHF was 1.729 +/- 0.114 for the experimental eye and 1.262 +/- 0.104 microliters.min-1 for the control eye (P less than or equal to 0.01). The pseudofacility tended to be higher in the terbutaline-treated eye (0.072 +/- 0.026 microliters.min-1.mmHg-1) than in the control eye (0.048 +/- 0.012 microliters.min-1.mmHg-1), but the difference was not statistically significant. There was no difference in total and true outflow facility between the experimental and control eye. The results indicate that the pressure sensitivity of the AHF is independent of the initial level of the AHF. VIP increases true outflow facility, possibly via a direct effect on the trabecular meshwork. VIP also appears to rise the IOP due to an increase in episcleral venous pressure, which could be secondary to vasodilatation in the anterior segment.