|Year : 1978 | Volume
| Issue : 3 | Page : 1-7
Dynamics of corneo-scleral envelope
Hari V Nema1, Calbert I Phillips2, Peter D Soden3, Janet Vale4
1 Benares Hindu University, India
2 Department of Ophthalmology; University of Edin, Scotland, United Kingdom
3 Department of Mechanical Engineering, Institute of Science and Technology, University of Manchester, England, United Kingdom
4 Department of Pharmacology, University of Manchester, England, United Kingdom
Calbert I Phillips
Department of Ophthalmology; University of Edin, Scotland
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Nema HV, Phillips CI, Soden PD, Vale J. Dynamics of corneo-scleral envelope. Indian J Ophthalmol 1978;26:1-7
|How to cite this URL:|
Nema HV, Phillips CI, Soden PD, Vale J. Dynamics of corneo-scleral envelope. Indian J Ophthalmol [serial online] 1978 [cited 2019 Dec 13];26:1-7. Available from: http://www.ijo.in/text.asp?1978/26/3/1/31186
The corneo-scleral envelope may not be the very stiff container of an incompressible fluid which we normally imagine. Changes in its absolute surface area, if they occur at all, would probably be slow and small, with very transient and unimportant changes in intraocular pressure. However, alterations in the collagen fibres in and around the canal of Schlemm and trabecular meshwork might make small but important and constant changes in facility of outflow.
In general, deductions from accepted premises are usually correct. But important advances tend to occur from a critical attitude to accepted premises. To take a fairly recent example from ophthalmology, we have long considered the corneo-scleral envelope to be water-tight until Bill showed it to be "leaky", although it is probably much more leaky (3 x) in monkeys because of their very thin sclera than in humans.
The notion that the corneo-scleral envelope might be a slightly dynamic structure arose as a possible means of explaining some inconsistencies in drug action of intraocular pressure: possibly there might be a "pharmaco-dynamics of sclera".
| Materials and Methods|| |
Parallel-sided strips of sclera approximately 4mm wide and 30mm long were cut from the equatorial region of cadaver human eyes which had been stored in "sterile" conditions for 9 to 22 days (at the time it was difficult to obtain younger specimens). The crosssectional area of each strip was calculated, thickness measurement was least accurate because some compression of the tissue by the standard micrometer even with a light ratchet spring was unavoidable. The two ends of the specimens were coated with Eastman's 910 adhesive and clamped. This assembly was placed in a 100 ml. bath containing test solutions at room temperature and clamped in the jaws of an Instron Tensile Tenting machine capable of giving a continuous record of load to an accuracy of + 0 5gm (Figure 1). The specimen was stretched at a rate of I mm/min. to a load of approximately 80gm and then allowed to relax without any change in length until reasonably steady conditions were achieved. A similar principle was used by Glaster, Perkins and Pommiers.
| Results|| |
In order to check that the mechanical upset of changing the solutions did not disturb the steady state, at the start of each experiment the 0.9% solution of saline was removed and replaced with an identical solution: no change in the "slope" of the tension curve resulted. We then showed that a change in the solution to pilocarpine caused a contraction of the scleral strip [Figure - 2].
We considered this finding critically and decided that osmotic pressure of the solution might explain away the apparent drug effect. So we embarked on a more basic series of observations on the effect of solutions of different osmotic pressures on the "relaxation" of the scleral strips.
As [Figure - 3] shows, when 2.7% NaCl replaced the 0.9% NaCI, the scleral strip "relaxed" but regained its tension when the 0.9% saline solution was used again. Consistently, the 0.45% solution produced a further contraction of the specimen.
The last three columns in [Table - 1] show the percentage change in tension of three specimens bathed in various concentrations of NaCl [Figure - 4]. All the results were consistent: "relaxation", i.e. reduction in tension, occurred when a more hypertonic saline replaced a less hypertonic saline and "contraction", i.e. increase in tension, occurred when the change in concentration was towards hypotonicity. The change in tension was reversible in all specimens. (Several other specimens were studied with similar results, but apart from one the tests were not systematic enough to justify inclusion: all the effects were consistent, and there was no evidence to suggest that the order in which solutions were changed had any effect.
There were three defects in the experiments reported in Part I viz:
(a) too great a lapse of time between removal of the (human cadaver) eyes and the experiments (9-22 days), (b) -the specimens examined were too few to allow statistical analysis and (c) the tensile stresses in the specimens of human sclera loaded with 80gm weight in Part I were approximately equal to those in a glaucomatous eye with an intraocular pressure of 75 mm Hg: a lesser load would be more realistic.
In order to circumvent some of these defects, fresh specimens of rabbit sclera were used for another series of experiments.
| Materials and Methods|| |
Equatorial Rings of Sclera. These were obtained from eyes of New Zealand white rabbits, enucleated after they were killed by a blow on the back of the neck. Muscles, fat etc. were trimmed off the surface of the eyeballs. With a scalpel, parallel grooves (3-4 mm apart) were made round the equator, and then scissors were used to cut out the rings. Forceps easily dislodged choroidal and retinal tissue from their inner surfaces. The rings were randomly allotted (toss of a coin) to the two different recording devices and the various saline concentrations; this ensured that, for example, no particular concentration of saline received all right eyes, although by chance right and left eyes from the same rabbit may have been allotted occasionally to the same concentration of saline (but never to the same transducer). Each ring was used only once. Sixteen rings were used for each of the four concentrations of saline and each of the two initial tensions (5gm and 10gm).
Concentrations of Saline used were 0.45%, 0.67%, 0.9% and 1.8% NaCl. Recording Devices. A strain guage transducer with a Rikadenki single channel pen recorder was used. Each equatorial ring of sclera was (a) at one looped round a pillar and (b) at the other end attached by a cotton thread to the transducer, and then (c) immersed in one of the saline solutions at 37°C. Tension was applied via the transducer at 5gm or 10gm Thus the scleral rings became in effect double strips of tissue. (A single strip was presumed to have rather fewer continuous lengths of collagen fibrils).
The changes in tension in each ring were continuously recorded for 2 hours 8 minutes.
| Results|| |
From the continuously recorded tension, the percentage residual tension in each loop was read off at 0.5, 1, 2, 4, 8, 16, 32, 64 and 128 mins. Means of the 16 observations at each concentration were obtained, together with standard errors, and graphs plotted of % tension remaining against time. [Figure - 5]. For all concentrations and both intitial tensions, the % tension remaining decreased exponentially with time. An analysis of variance showed that for both the 5 gm and 10 gm intitial tensions, the scleral loops immersed in 0.45% saline had a significantly lower rate of loss of tension than the loops immersed in 0.9% saline [Table - 2].
At 10 gm initial tension, a significant difference was found at 0.45% NaCl. and 0.67' NaCl. Rather surprisingly, the difference between strips in 1.8% saline and 0.9% saline was far from significant: [Table - 3].
| Discussion|| |
It is interesting to note that the results observed with isolated human scleral strips assessed by one method (Part I) were reasonably consistent with the results observed in isolated loops of fresh rabbit sclera assessed by a different method (Part II) except for the similarity of behaviours of rabbit sclera in 1.9% and 0.9% saline. Although Saiduzzafar found an increase in K (ocular rigidity) in intact enucleated cadaver eyeballs with increasing osmotic pressure of the immersing solution, she used 6% dextran (hypertonic) for comparison with 0.9% saline; her experiments related to an immediate effect on eyeball distension whereas ours related to the "relaxation" of a stretched strip, and there are other possible explanations for the apparent discrepancy between her results and ours.
| Mechanism of Effect|| |
At the level of the individual components of sclera, how does a relatively low concentration of NaCI in solution make the sclera retain its tension better than in relatively higher concentration? The likeliest explanation is some effect on the constituent molecules in the collagen fibrils: the details are conjectural. Similarly an effect in the inter-fibril substance(s) may be operative. At a more superficial level, the low concentration of salt solution may make the scleral strips "absorb" more water thereby parting the individual fibres more, and so increasing (or reducing the decrease in) the tension: this effect could work via the inter-fibril substance(s) or merely on the fluid between fibrils.
| Possible Relevance|| |
Subject to various reservations to be mentioned below, do these observations have any relevance to the human eyeball in vivo? Although variations in osmotic pressure of blood and tissue fluid occur, nature tries to minimise these. However, some residual variations remain. When a fall in osmotic pressure occurs in blood and tissue fluid, for example in the water drinking test, then there occurs a rise in intraocular pressure, at least at first. This would tend to produce an enlargement of the eyeball, with some myopia, but such an affect would be minimised by the increased tension in the sclera which we have observed. A disadvantage teleologically of these circumstances, if they be true, is that intraocular pressure would be expected to rise even more, but change; in choroidal blood volume could easily compensate, a! seems very likely, such a compensation would also tent to neutralise the myopia.
Our observations would suggest that after a water drinking test there would be a "stiffening" in the corneoscleral envelope, yet Drance found a fall in ocular rigidity. Assuming these latter observations to be valid, the increase in intraocular volume presumably occurring on water drinking may account for the decrease it rigidity-volume variations being probably an important component of ocular rigidity".
| Variations in Blood and Tissue Fluid Osmolality|| |
The NaCl concentrations we used were "normal" (0.9% exerting 300m. osmols/Kg water and +100%, +200% and -50% of that concentration. -quite unphysiological, so that there must remain doubt whether variations actually occurring in vivo would alter the physical size and tension of the corneo-scleral envelope.
Variations in osmolality of tissue fluid presumably follow those of serum but possibly with reduced magnitude. Serum osmolality has been found to vary by up to + 14% in diabetes in and down to -14% in compulsive water drinkers when compared with the mean normal of 280m. osmols per Kg (range 273-289). By various solutions serum osmolality has been raised by as much as+20% in humans. A rise in blood osmolality of about 10% has been observed after intravenous urea and in serum osmolality of up to 10% after mannitol, glycerin or urea a "relaxation" of the cornescleral envelope may explain part of their hypothesis deffect.
| Pharmacodynamies of Coreno-Scleral Envelope|| |
As has been mentioned earlier the hypothesis which led to these present studies was that pilocarpine might affect ocular tension to a small extent by causing "contraction" or "relaxation" of collagen fibres in the anterior half of the globe, especially around the canal of Schlemm including the trabecular meshwork, as well as by its effect on the ciliary muscle. However some preliminary experiments have shown no effect from a wide range of concentrations of pilocarpine, adrenalin, nor-adrenalin, isoprenaline, acetylcholine and histamine.
Experiments on isolated tunica albuginea of rabbits' testes have shown that acetylcholine and to a lesser extent nor-adrenalin cause the tissue to contract, maximally in two minutes, followed by relaxation, presumably smooth muscle in the tunica albuginea (as the authors suggest) explain the behaviour of that tissue, and its difference from the behaviour of sclera.
| Experimental Methods|| |
For simplicity uniaxial tension was applied to straightened strips originally curved but we consider that the results would be applicable in principle in vivo . In general, probably a more precise experimental method could be devised to measure smaller changes in tension in concentrations of saline less different from 0.9%.
| Further Speculation|| |
We suggest that a simple mechanism by which outflow of aqueous humour may alter with increasing distension of the eyeball lies in a change in the angle between cornea and sclera, with resultant change in "stretching" of the trabecular meshwork. At very high pressures the angle between cornea and sclera may well become flattened, loosening the trabecular meshwork to allow it to become impact in collector channels on the opposite side of the canal of Schlemm. Initially as intraocular pressure begins to rise it could be that the meshwork is stretched (because of a more acute angle between cornea and sclera) with improved outflow of aqueous humour a la pilocarpine.
| Summary|| |
Parallel-sided strips of sclera from human cadavers were clamped in the jaws of an Instron Tensile Testing Machine, immersed in 0.9% NaCl solution of pH 6.4 at room temperature and stretched to a load of 80 gm., then allowed to relax without change in length until reasonably steady conditions were obtained. Replacing 0.9% NaCl with a solution of 1.8% or 2.7% NaCl caused a decrease in tension while 0.45% NaCl caused an increase in tension.
Equatorial rings of sclera from rabbit eyes were (a) looped round a pillar at one end and (b) at the other end attached to a strain gauge transducer, and (c) immersed in saline solutions of 0.45, 0.675, 0.9 and 1.8% concentrations in a tissue bath at 37°C. After 10 mins. for equilibration, a tension of 5gm or 10gm was applied to the rings and the change in tension was recorded at 0.5, 1, 2, 4, 8, 16, 32, 64 and 128 minutes. Each ring was used only once.
The tension decreased exponentially in all cases, more for the 10gm weight than for the 5gm weight. The decrease in tension, and its rate of decline, were significantly less when the rings (16) were maintained in 0.45% saline in comparison with 0.9% saline (16 rings). Although the decrease and its rate to decline was also less in 0.9% than in 1.8% saline, the difference between these two was not significant.
Experiments were not done at more "physiological" concentrations because small changes were difficult to record with this equipment. It may well be that no changes occur in the corneo-scleral envelope in vivo over the physiological range, and even if they do, changes in intra-ocular blood volume can quickly compensate for them.
No effect was found from a wide range of concentrations of pilocarpine, adrenalin, noradrenalin, isoprenaline, acetylcholine and histamine.
However we suggest on present evidence that the corneo-scleral envelope may not be an entirely passive container, (as also the collagen frame-work around the trabecular meshwork) a factor which should be considered when the physiology and pharmacology of changes in intra-ocular pressure are being considered.
| References|| |
Barlow, E.D. and de Wardener, H.E., 1959, Quart. J. Med.,
Bill, A., 1965, Invest. Ophthal., 4,
Bill, A. and Phillips, C.I., 1971, Exp. Eye Res., 12,
Davis, J.R. and Langford, G.A., 1969, Nature, 222.
Drance, S.M., 1963. A.M.A. Arch. Ophthal., 69,
Duncan, L.S., Elus, P.P. and Paterson, C.A., 1970, Exp. Eye Res., 10,
Galin, M.A., Aizawa, F. and Mclean, J.M., 1959, A.M.A. Arch. Ophthal., 62,
Gloster, J., Perkins, E.S. and Pommier, Maire Louise, 1957, Brit. J. Ophthal., 41,
Grierson, I and Lee, W.R., 1974, Exp. Eye Res., 19,
Phillips, C.I., 1971, Brit. J. Physiol. Optics, 26,
Phillips, C.I. and Shaw, T.L., 1970, Exp. Eye Res,
Rapoport, S., West C.D. and Bradsky, W.A., 1949, Amer. J. Physiol.,
Saiduzzafar, Hamida., 1962, Brit. J. Ophthal., 46,
Soden, P.D. and Kershaw, I, 1974, Medical and Biological Engineering, 22,
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]
[Table - 1], [Table - 2], [Table - 3]